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{{Taxobox
{{Taxobox
| color = lightgrey
| name = ''Bacillus anthracis''
| name = ''Bacillus anthracis''
| image = Bacillus_anthracis_01.png
| image = Bacillus_anthracis.png
| image_width = 240px
| image_width = 240px
| image_caption = Photomicrograph of ''Bacillus anthracis'' (fuchsin-methylene blue spore stain).
| image_caption = Photomicrograph of ''Bacillus anthracis'' (fuchsin-methylene blue spore stain)
| regnum = [[Bacterium|Bacteria]]
| domain = [[Bacterium|Bacteria]]
| kingdom = [[Archaebacteria]]
| phylum = [[Firmicutes]]
| phylum = [[Firmicutes]]
| classis = [[Bacilli]]
| classis = [[Bacilli]]
Line 15: Line 15:
| binomial_authority = Cohn 1872
| binomial_authority = Cohn 1872
}}
}}
[[Image:B_anthracis_diagram_en.png|right|thumb|240px|Structure of ''Bacillus anthracis''.]]
__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{JH}}
{{About0|Anthrax}}
 
{{Anthrax}}
{{CMG}}
==Overview==
==Overview==
'''''Bacillus anthracis''''' is a [[Gram-positive]], [[Facultative anaerobic organism|facultatively anaerobic]], rod-shaped [[bacterium]] of the genus ''[[Bacillus]]''. An [[endospore]] forming bacterium, ''B. anthracis'' is a natural soil-dwelling organism, as well as the causative agent of [[anthrax disease|anthrax]].<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | isbn = 0-8385-8529-9 }}</ref>
The causative agent of [[anthrax]] is [[B. anthracis]], a [[motility|nonmotile]], [[Gram-positive]], [[aerobic]] or facultatively [[anaerobic]], [[endospore]]-forming, [[rod]]-shaped [[bacterium]]. The [[spores]] of [[B. anthracis]], which can remain dormant in the environment for decades, are the [[infectious]] form, but this vegetative [[B. anthracis]] rarely causes disease.<ref>{{Cite journal | author = [[Sean V. Shadomy]] & [[Theresa L. Smith]] | title = Zoonosis update. Anthrax | journal = [[Journal of the American Veterinary Medical Association]] | volume = 233 | issue = 1 | pages = 63–72 | year = 2008 | month = July | doi = 10.2460/javma.233.1.63 | pmid = 18593313}}</ref> The [[Bacillus]] may enter the body through the [[skin]], [[lungs]], [[gastrointestinal system]] or by injection, after which they will travel to the [[lymph nodes]]. The [[virulence factor]]s will facilitate the translocation of the [[toxins]] to the [[cytosol]]. The [[natural reservoir]]s of [[Bacillus anthracis]] include humans, mammals, herbivores, reptiles, and birds.
 
Each cell is about 1 by 6 [[micrometre|μm]] in size.
 
==Historical background==
''B. anthracis'' was the first bacterium conclusively demonstrated to cause disease, by [[Robert Koch]] in 1877.<ref name=Brock>{{cite book | author = Madigan M, Martinko J (editors). | title = Brock Biology of Microorganisms | edition = 11th ed. | publisher = Prentice Hall | year = 2005 | isbn = 0-13-144329-1 }}</ref> The species name ''anthracis'' is from the [[Greek language|Greek]] ''anthrakis'' (ἄνθραξ), meaning ''coal'' and referring to the most common form of the disease, [[cutaneous]] anthrax, in which large black skin [[lesion]]s are formed.
 
==Pathogenicity==
Under conditions of environmental stress, ''B. anthracis'' bacteria naturally produce endospores which rest in the soil and can survive for decades in this state.  When ingested by a cattle, sheep, or other [[herbivore]]s, the bacteria begin to reproduce inside the animal and eventually kill it, then continue to reproduce in its carcass.  Once the nutrients are exhausted, new endospores are produced and the cycle repeats.<ref name=Baron>{{cite book | author = Turnbull PCB | title = Bacillus. ''In:'' Barron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.925 | isbn = 0-9631172-1-1}}</ref>
 
''B. anthracis'' has at least 89 known [[strain (biology)|strains]], ranging from highly virulent strains with [[biological warfare]] and [[bioterrorism]] applications ([[Ames strain|Ames]] and ''Vollum'') to benign strains used for [[inoculation]]s (''Sterne''). The strains differ in presence and activity of various [[gene]]s, determining their [[virulence]] and production of [[antigen]]s and [[toxin]]s. The form associated with the [[2001 anthrax attacks]] produced both [[anthrax toxin|toxin]] (consisting of three [[protein]]s: [[anthrax toxin|the protective antigen, the edema factor and the lethal factor]]) and a [[Capsule_(microbiology)|capsule]] (consisting of a polymer of glutamic acid).  Infection with anthrax requires the presence of all three of these exotoxins.<ref>{{cite journal |author=Dixon TC, Meselson M, Guillemin J, Hanna PC |title=Anthrax |journal=N. Engl. J. Med. |volume=341 |issue=11 |pages=815-26 |year=1999 |pmid=10477781 |doi=}}</ref>
 
The bacterium can be cultivated in ordinary nutrient medium under aerobic or anaerobic conditions.
 
==Treatment==
{{main|Anthrax}}
Infections with ''B. anthracis'' can be treated with [[Beta-lactam|β-lactam]] [[antibiotic]]s such as [[penicillin]], and others which are active against Gram-positive bacteria.<ref>{{cite journal |author = Barnes JM |title=Penicillin and ''B. anthracis''. |journal= J Path Bacteriol |volume=194|year=1947|pages=113}}</ref>
 
==Treatment==
 
===Antimicrobial therapy===
 
:* [[Bacillus anthracis]], treatment
::* (A) '''Treatment for cutaneous anthrax, without systemic involvement'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
:::* Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown): [[Ciprofloxacin]] 500 mg PO q12h {{or}} [[Doxycycline]] 100 mg PO q12h {{or}} [[Levofloxacin]] 750 mg PO q24h {{or}} [[Moxifloxacin]] 400 mg PO q24h
:::* Alternative regimen: [[Clindamycin]] 600 mg PO q8h {{or}} [[Amoxicillin]] 1 g PO q8h (for penicillin-susceptible strains) {{or}} [[Penicillin VK]] 500 mg PO q6h (for penicillin-susceptible strains)
:::: Note: Duration of treatment is 60 days for bioterrorism-related cases and 7-10 days for naturally acquired cases.
 
::* (B) '''Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
:::* (B-1) '''Systemic anthrax with possible/confirmed meningitis'''
::::* (1) Bactericidal agent (fluoroquinolone): '''[[Ciprofloxacin]] 400 mg IV q8h''' ({{or}} [[Levofloxacin]] 750 mg IV q24h {{or}} [[Moxifloxacin]] 400 mg IV q24h) {{and}}
::::* (2) Bactericidal agent (β-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown: '''[[Meropenem]] 2 g IV q8h''' {{or}} [[Imipenem]] 1 g IV q6h {{or}} [[Doripenem]] 500 mg IV q8h {{or}} [[Penicillin G]] 4 MU IV q4h (for penicillin-susceptible strains) {{or}} [[Ampicillin]] 3 g IV q6h (for penicillin-susceptible strains) {{and}}
::::* (3) Protein synthesis inhibitor: '''[[Linezolid]] 600 mg IV q12h''' {{or}} [[Clindamycin]] 900 mg IV q8h {{or}} [[Rifampin]] 600 mg IV q12h {{or}} [[Chloramphenicol]] 1 g IV q6-8h
::::: Note (1): Duration of treatment: ≥ 2-3 weeks until clinical criteria for stability are met (Preferred drugs are indicated in boldface).
::::: Note (2): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
::::: Note (3): Alternative drugs are listed in order of preference for treatment for patients who cannot take first-line treatment, or if first-line treatment is unavailable.
::::: Note (4): Increased risk for seizures associated with [[Imipenem]]/[[Cilastatin]] treatment.
::::: Note (5): [[Linezolid]] should be used with caution in patients with thrombocytopenia because it might exacerbate it. [[Linezolid]] use for > 14 days has additional hematopoietic toxicity.
::::: Note (6): [[Rifampin]] is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.
::::: Note (7): [[Chloramphenicol]] should only be used if other options are not available because of toxicity concerns.
 
:::* (B-2) '''Systemic anthrax when meningitis has been excluded'''
::::* (1) Bactericidal agent: '''[[Ciprofloxacin]] 400 mg IV q8h''' {{or}} [[Levofloxacin]] 750 mg IV q24h {{or}} [[Moxifloxacin]] 400 mg q24h {{or}} [[Meropenem]] 2 g IV q8h {{or}} [[Imipenem]] 1 g IV q6h {{or}} [[Doripenem]] 500 mg IV q8h {{or}} [[Vancomycin]] 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) {{or}} [[Penicillin G]] 4 MU IV q4h (penicillin-susceptible strains) {{or}} [[Ampicillin]] 3 g IV q6h (penicillin-susceptible strains) {{and}}
::::* (2) Protein synthesis inhibitor: '''[[Clindamycin]] 900 mg IV q8h''' {{or}} '''[[Linezolid]] 600 mg IV q12h''' {{or}} [[Doxycycline]] 200 mg IV initially, then 100 mg IV q12h {{or}} [[Rifampin]] 600 mg IV q12h
::::: Note (1): Duration of treatment: for 2 weeks until clinical criteria for stability are met (Preferred drugs are indicated in boldface).
::::: Note (2): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
::::: Note (3): Alternative drugs are listed in order of preference for treatment for patients who cannot take first-line treatment, or if first-line treatment is unavailable.
::::: Note (4): Increased risk for seizures associated with [[Imipenem]]/[[Cilastatin]] treatment.
::::: Note (5): [[Linezolid]] should be used with caution in patients with thrombocytopenia because it might exacerbate it. [[Linezolid]] use for > 14 days has additional hematopoietic toxicity.
::::: Note (6): [[Rifampin]] is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.
::::: Note (7): A single 10-14 days course of [[Doxycycline]] is not routinely associated with tooth staining.
 
::* Specific considerations
:::* '''Treatment of anthrax for pregnant Women''' 
::::* (A) Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis <ref name="pmid24457117">{{cite journal| author=Meaney-Delman D, Zotti ME, Creanga AA, Misegades LK, Wako E, Treadwell TA et al.| title=Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages=  | pmid=24457117 | doi=10.3201/eid2002.130611 | pmc=PMC3901460 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24457117  }} </ref>
:::::* (1)''' A Bactericidal Agent (Fluoroquinolone)''': '''[[Ciprofloxacin]]''' 400 mg IV q8h is preferred, {{or}}  [[Levofloxacin]] 750 mg IV q24h, {{or}}
:::::* (2).''' A Bactericidal Agent (β-lactam)'''
::::::* (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : '''[[Meropenem]] 2 g q8h''',{{or}}
::::::* (b). Alternatives for penicillin-susceptible strains: [[Ampicillin]] 3 g IV q6h,{{or}} [[Penicillin G]] 4 million units IV q4h, {{or}}
:::::* (3).''' A Protein Synthesis Inhibitor''': '''[[Clindamycin]] 900 IV mg q8h''',{{or}}  [[Rifampin]] 600 IV mg q12h
:::::: Note (1): At least one antibiotic with transplacental passage is recommended.
:::::: Note (2): Duration of treatment is for ≥2–3 weeks until clinical criteria for stability are met. Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
 
::::* (B) Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded
:::::* (1).''' A Bactericidal Antimicrobial''': '''[[Ciprofloxacin]] 400 mg IV q8h''' is preferred, {{or}}  [[Levofloxacin]] 750 mg IV q24h, {{or}}
:::::* (2).''' A Bactericidal Agent (β-lactam)'''
::::::* (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : '''[[Meropenem]] 2 g q8h''',{{or}}
::::::* (b). Alternatives for penicillin-susceptible strains:[[Ampicillin]] 3 g IV q6h,{{or}} [[Penicillin G]] 4 million units IV q4h, {{or}}
:::::* (3).''' A Protein Synthesis Inhibitor''':[[Clindamycin]] 900 IV mg q8h,{{or}}  [[Rifampin]] 600 IV mg q12h
::::::Note (1): At least one antibiotic with transplacental passage is recommended.
::::::Note (2):Duration of treatment: for ≥2 weeks until clinical criteria for stability are met. Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness
 
::::*(C) Oral antimicrobial treatment for cutaneous anthrax without systemic involvement
:::::* (a).For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: '''[[Ciprofloxacin]] 400 mg IV q8h''' is preferred.
::::::Note (1): duration of treatment is 60 days
::::::Note (2): Recommendations are specific to cutaneous anthrax in the setting of bioterrorism.
 
:::* '''Treatment for anthrax in childern''' <ref name="pmid24777226">{{cite journal| author=Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D et al.| title=Pediatric anthrax clinical management. | journal=Pediatrics | year= 2014 | volume= 133 | issue= 5 | pages= e1411-36 | pmid=24777226 | doi=10.1542/peds.2014-0563 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24777226  }} </ref>
::::* '''(1). Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)'''
:::::* (A). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : '''[[Ciprofloxacin]], 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose)''' {{or}} [[Doxycycline]], <45 kg: 4.4 mg/kg/day, PO, divided q12h (not to exceed 100 mg/dose) ≥45 kg: 100 mg/dose, PO, given q12h {{or}} [[Clindamycin]], 30 mg/kg/day, PO, divided q8h (not to exceed 600 mg/dose) {{or}} [[Levofloxacin]] <50 kg: 16 mg/kg/day, PO, divided q12h (not to exceed 250 mg/dose) >50 kg: 500 mg, PO, given q24h {{or}}
 
:::::* (B). Alternatives for penicillin-susceptible strains: '''[[Amoxicillin]], 75 mg/kg/day, PO, divided q8h (not to exceed 1 g/dose)''' {{or}} [[Penicillin VK]], 50-75 mg/kg/day, PO, divided q6h to q8h
:::::: Note (1): Duration of therapy for naturally acquired infection: 7-10 days and for a biological weapon-related event: will require additional prophylaxis for inhaled spores, to complete an antimicrobial course of up to 60 days from onset of illness.
:::::: Note (2): Bold font for preferred antimicrobial agent.
:::::: Note (3): Normal font for alternative selections are listed in order of preference for therapy for patients who cannot take first-line therapy or first-line therapy is unavailable.
:::::: Note (4): Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.
:::::: Note (5): Italicized font indicates FDA approval for the indication in the pediatric population.
:::::: Note (6): A single 10- to 14-day course of doxycycline is not routinely associated with tooth staining.
:::::: Note (7): Be aware of the possibility of emergence of penicillin-resistance during monotherapy with amoxicillin or penicillin.
 
::::* '''(2). Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)'''
:::::* (A). A bactericidal antimicrobial
::::::* (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: '''[[Ciprofloxacin]], 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose)''' {{or}} [[Meropenem]], 60 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) {{or}} [[Levofloxacin]] <50 kg: 20 mg/kg/day, IV, divided q12h (not to exceed 250 mg/dose >50 kg: 500 mg, IV, q24h {{or}} [[Imipenem]]/[[Cilastatin]],a 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) {{or}} [[Vancomycin]], 60 mg/kg/day, IV, divided q8h (follow serum concentrations)
::::::* (b). Alternatives for penicillin-susceptible strains: '''[[Penicillin G]], 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose)''' {{or}} [[Ampicillin]], 200 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) {{and}}
 
:::::* (B). A Protein Synthesis Inhibitor: '''[[Clindamycin]], 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose)''' {{or}} [[Linezolid]] (non-CNS infection dose): <12 y old: 30 mg/kg/day, IV, divided q8h ≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) {{or}} [[Doxycycline]] <45 kg: 4.4 mg/kg/day, IV, loading dose (not to exceed 200 mg); ≥45 kg: 200 mg, IV, loading dose then <45 kg: 4.4 mg/kg/day, IV, divided q12h  (not to exceed 100 mg/dose); ≥45 kg: 100 mg, IV, given q12h {{or}} Rifampin,d 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose)
:::::: Note (1): Duration of therapy for 14 days or longer until clinical criteria for stability are met.Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
:::::: Note (2): Systemic anthrax includes inhalation anthrax; injection, gastrointestinal, or cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck.
:::::: Note (3): Children with altered mental status, signs of meningeal inflammation, or focal neurologic deficits should be considered to have CNS infection if CSF examination is not possible. A normal CSF may not completely exclude deep brain hemorrhage/abscess.
:::::: Note (4): Bold font for preferred antimicrobial agent.
:::::: Note (5): Normal font for  alternative selections are listed in order of preference for therapy for patients who cannot tolerate first-line therapy or if first-line therapy is unavailable.
:::::: Note (6): Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.
:::::: Note (7): Increased risk of seizures associated with [[Imipenem]]/[[Cilastatin]] therapy.
:::::: Note (8): [[Linezolid]] should be used with caution in patients with thrombocytopenia, as it may exacerbate it.[[Linezolid]] use for >14 days carries additional hematopoietic toxicity.
:::::: Note (9): A single 14-day course of [[Doxycycline]] is not routinely associated with tooth staining.
:::::: Note (10): [[Rifampin]] is not a protein synthesis inhibitor; it may also be used in combination therapy based on in vitro synergy
 
::::* '''(3).Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older'''
:::::* (A). A bactericidal antimicrobial (fluoroquinolone): [[Ciprofloxacin]], 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose){{or}} [[Levofloxacin]] <50 kg: 16 mg/kg/day, IV, divided q12h (not to exceed 250 mg/dose); >50 kg: 500 mg, IV, q24h {{or}} [[Moxifloxacin]] 3 months to <2 years: 12 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose)
:::::: 2-5 years: 10 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose)
::::::6–11 years: 8 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose)
:::::: 12–17 years, ≥45 kg body weight: 400 mg, IV, once daily
:::::: 12–17 years, <45 kg body weight: 8 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose) {{and}}
 
:::::* (B). A bactericidal antimicrobial (β-lactam or glycopeptide)
::::::* (a). For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown : [[Meropenem]], 120 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) {{or}} [[Imipenem]]/[[Cilastatin]], 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) {{or}} [[Doripenem]], 120 mg/kg/day, IV, divided q8h (not to exceed 1 g/dose) {{or}} [[Vancomycin]], 60 mg/kg/day, IV, divided q8h
::::::* (b). Alternatives for penicillin-susceptible strains: [[Penicillin G]], 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose) {{or}} [[Ampicillin]], 400 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) {{and}}
 
::::::* (C). A Protein Synthesis Inhibitor: [[Linezolid]] <12 y old: 30 mg/kg/day, IV, divided every 8 h≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) {{or}} [[Clindamycin]], 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose)  {{or}} [[Rifampin]], 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose)  {{or}} [[Chloramphenicol]], 100 mg/kg/day, IV, divided q6h
::::::: Note (1): Duration of therapy for 2–3 wk or greater, until clinical criteria for stability are met.Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
::::::: Note (2): Systemic anthrax includes anthrax meningitis; inhalation anthrax; or injection, gastrointestinal, and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck.
::::::: Note (3): Children with altered mental status, signs of meningeal inflammation, or focal neurologic deficits should be considered to have CNS infection if CSF examination is not possible. Normal CSF may not completely exclude deep brain hemorrhage/abscess.
::::::: Note (4): Bold font for preferred antimicrobial agent.
::::::: Note (5): Normal font for alternative selections are listed in order of preference for therapy for patients who cannot tolerate first-line therapy or if first-line therapy is unavailable.
::::::: Note (6): Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.
::::::: Note (7):  A 400-mg dose of [[Ciprofloxacin]], IV, provides an equivalent exposure to that of a 500-mg ciprofloxacin oral tablet.
::::::: Note (8): Increased risk of seizures associated with [[Imipenem]]/[[Cilastatin]] therapy.
::::::: Note (9): [[Doripenem]] is approved in Japan at this dose for the treatment of community-acquired bacterial meningitis.
::::::: Note (10): [[Linezolid]] should be used with caution in patients with thrombocytopenia, as it may exacerbate it. Linezolid use for >14 days carries additional hematopoietic toxicity.
::::::: Note (11): [[Rifampin]] is not a protein synthesis inhibitor; it may also be used in combination therapy based on in vitro synergy for some strains of staphylococci. Not evaluated for Bacillus anthracis.
::::::: Note (12) : [[Chloramphenicol]] Should be used only if other options are not available, because of toxicity concerns.
 
::::* (4).'''Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)'''
:::::* (A). A bactericidal antimicrobial
:::::: (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: [[Ciprofloxacin]], 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose) {{or}} [[Levofloxacin]] <50 kg: 16 mg/kg/day, PO, divided q12h (not to exceed 250 mg/dose) ≥50 kg: 500 mg, PO, given q24h {{or}}
:::::: (b). Alternatives for penicillin-susceptible strains: [[Amoxicillin]], 75 mg/kg/day, PO, divided q8h (not to exceed 1 g/dose) {{or}} [[Penicillin VK]], 50–75 mg/kg/day, PO, divided q6h-q8h {{and}}
 
:::::* (B). A protein synthesis inhibitor: [[Clindamycin]] 30 mg/kg/day, PO, divided q8h (not to exceed 600 mg/dose) {{or}} [[Doxycycline]] <45 kg: 4.4 mg/kg/day, PO, divided q12h (not exceed 100 mg/dose) ≥45 kg: 100 mg, PO, given q12h {{or}} [[Linezolid]] (non-CNS infection dose):
:::::: <12 y old: 30 mg/kg/day, PO, divided q8h
:::::: ≥12 years old: 30 mg/kg/day, PO, divided q12h (not to exceed 600 mg/dose)
::::::: Note (1): Duration of therapy to complete a treatment course of 14 days or greater. May require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
::::::: Note (2): Severe anthrax includes inhalation anthrax; injection, gastrointestinal, or cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck.
::::::: Note (3): Bold font for  preferred antimicrobial agent.
::::::: Note (4): Normal font for alternative selections are listed in order of preference for therapy for patients who cannot take first-line therapy or if first-line therapy is unavailable.
::::::: Note (5): Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.
::::::: Note (6):  A single 14-day course of doxycycline is not routinely associated with tooth staining.
::::::: Note (7): [[Linezolid]] should be used with caution in patients with thrombocytopenia, as it may exacerbate it. [[Linezolid]] use for >14 days carries additional hematopoietic toxicity.
 
::::* (5).''' Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)'''
:::::* (A). Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)
::::::* (1). '''Bactericidal antimicrobial (fluoroquinolone) therapy'''
:::::::* (a) For 32–34 weeks gestational age 
:::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 5 mg/kg/day, q24h
:::::::: For 1–4 weeks of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 5 mg/kg/day, q24h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 wk of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 5 mg/kg/day, q24h
:::::::: For 1–4 wk of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 5 mg/kg/day, q24h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] IV 30 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 10 mg/kg/day, q24h
:::::::: For 1–4 weeks of Age : '''[[Ciprofloxacin]] IV 30 mg/kg/day, divided q12h''' {{or}} [[Moxifloxacin]] IV 10 mg/kg/day, q24h {{and}}
 
::::::* (2). '''A bactericidal antimicrobial (β-lactam)'''
:::::::* a. For all strains, regardless of penicillin susceptibility or if susceptibility is unknown :
::::::::* (a) For 32–34 weeks gestational age
::::::::: For 0–1 week of Age : '''[[Meropenem]]''' IV 60 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 50 mg/kg/day, divided q12h {{or}} [[Doripenem]] IV 20 mg/kg/day, divided q12h
::::::::: For 1–4 wk of Age : '''[[Meropenem]]''' IV 90 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 75 mg/kg/day, divided q8h {{or}} [[Doripenem]] IV 30 mg/kg/day,divided q8h
::::::::* (b) For 34–37 week gestational age
::::::::: For 0–1 week of Age : '''[[Meropenem]]''' IV 60 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 50 mg/kg/day, divided q12h {{or}} [[Doripenem]] IV 20 mg/kg/day, divided q12h
::::::::: For 1–4 week of Age : '''[[Meropenem]]''' IV 90 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 75 mg/kg/day, divided q8h {{or}} [[Doripenem]] IV 30 mg/kg/day,divided q8h
::::::::* (c) Term Newborn Infant
::::::::: For 0–1 week of Age: '''[[Meropenem]]''' IV 60 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 50 mg/kg/day, divided q12h {{or}} [[Doripenem]] IV 20 mg/kg/day, divided q12h
::::::::: For 1–4 week of Age : '''[[Meropenem]]''' IV 90 mg/kg/day, divided q8h {{or}} [[Imipenem]] IV 75 mg/kg/day, divided q8h {{or}} [[Doripenem]] IV 30 mg/kg/day,divided q8h {{or}}
:::::::* b. Alternatives for penicillin-susceptible strains
::::::::* (a) For 32–34 weeks gestational age
::::::::: For 0–1 week of Age : '''[[Penicillin G]]''' 200000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 100 mg/kg/day divided q12h,
::::::::: For 1–4 week of Age : '''[[Penicillin G]]''' 300000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 150 mg/kg/day divided q12h,
::::::::* (b) For 34–37 week gestational age
::::::::: For 0–1 week of Age : '''[[Penicillin G]]''' 300000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 150 mg/kg/day divided q12h,
::::::::: For 1–4 week of Age : '''[[Penicillin G]]''' 400000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 200 mg/kg/day divided q12h,
::::::::* (c) Term Newborn Infant
::::::::: For 0–1 week of Age : '''[[Penicillin G]]''' 300000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 150 mg/kg/day divided q12h,
::::::::: For 1–4 week of Age : '''[[Penicillin G]]''' 400000 Units/kg/day divided q12h,{{or}} [[Ampicillin]] 200 mg/kg/day divided q12h, {{and}}
 
::::::* (3).'''A protein synthesis inhibitor'''
:::::::* (a) For 32–34 weeks gestational age
:::::::: For 0–1 week of Age : '''[[Linezolid]]''' 20 mg/kg/day,divided q12h, {{or}} [[Clindamycin]] 10 mg/kg/day,divided q12h {{or}} [[Rifampin]] 10 mg/kg/day,divided q12h , {{or}} [[Chloramphenicol]] 25 mg/kg/day,q24h
:::::::: For 1–4 week of Age : '''[[Linezolid]]''' 30 mg/kg/day,divided q8h, {{or}} [[Clindamycin]] 15 mg/kg/day,divided q8h {{or}} [[Rifampin]] 10 mg/kg/day,divided q12h, {{or}} [[Chloramphenicol]] 50 mg/kg/day,q12h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 week of Age : '''[[Linezolid]]''' 30 mg/kg/day,divided q8h, {{or}} [[Clindamycin]] 15 mg/kg/day,divided q8h {{or}} [[Rifampin]] 10 mg/kg/day,divided q12h, {{or}} [[Chloramphenicol]] 25 mg/kg/day,q24h
:::::::: For 1–4 week of Age : '''[[Linezolid]]''' 30 mg/kg/day,divided q8h, {{or}} [[Clindamycin]] 20 mg/kg/day,divided q6h {{or}} [[Rifampin]] 10 mg/kg/day,divided q12h, {{or}} [[Chloramphenicol]] 50 mg/kg/day,q12h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : '''[[Linezolid]]''' 30 mg/kg/day,divided q8h, {{or}} [[Clindamycin]] 15 mg/kg/day,divided q8h {{or}} [[Rifampin]] 10 mg/kg/day,divided q12h, {{or}} [[Chloramphenicol]] 25 mg/kg/day,q24h
:::::::: For 1–4 week of Age : '''[[Linezolid]]''' 30 mg/kg/day,divided q8h, {{or}} [[Clindamycin]] 20 mg/kg/day,divided q6h {{or}} {[Rifampin]] 20 mg/kg/day,divided q12h, {{or}} [[Chloramphenicol]] 50 mg/kg/day,q12h
:::::::: Note :Duration of therapy For ≥2–3 week, until clinical criteria for stability are met. Will require prophylaxis to complete an antibiotic course of upto 60 days from onset of illness.
 
:::::* (B). Therapy for severe anthrax when meningitis can be ruled out
::::::* (1).'''A bactericidal antimicrobial'''
::::::: (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
::::::::* (a) For 32–34 weeks gestational age
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day,divided q12h''' {{or}} [[Meropenem]] IV 40 mg/kg/day,divided q8h {{or}} [[Imipenem]] IV 40 mg/kg/day,divided q12h
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day,divided q12h'''  {{or}}  [[Meropenem]] IV 60 mg/kg/day,divided q8h {{or}} [[Imipenem]] 50 mg/kg/day,divided q12h
::::::::* (b) For 34–37 week gestational age
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day,divided q12h''' {{or}}  [[Meropenem]] IV 60 mg/kg/day,divided q8h {{or}} [[Imipenem]] 50 mg/kg/day,divided q12h
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] IV 20 mg/kg/day,divided q12h''' {{or}}  [[Meropenem]] IV 60 mg/kg/day,divided q8h {{or}}  [[Imipenem]] 75 mg/kg/day,divided q8h
::::::::* (c) Term Newborn Infant
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] IV 30 mg/kg/day,divided q12h''' {{or}}  [[Meropenem]] IV 60 mg/kg/day,divided q8h {{or}}  [[Imipenem]] 50 mg/kg/day,divided q12h
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] IV 30 mg/kg/day,divided q12h''' {{or}}  [[Meropenem]] IV 60 mg/kg/day,divided q8h {{or}} [[Imipenem]] 75 mg/kg/day,divided q8h {{or}}
::::::::: [[Vancomycin]] IV (dosing based on serum creatinine for infants ≥32 wk gestational age). Follow vancomycin serum concentrations to modify dose.
:::::::::: If  Serum creatinine <0.7 then [[Vancomycin]] IV 15 mg/kg/dose q12h
:::::::::: If Serum creatinine 0.7 -0.9 then  [[Vancomycin]] IV 20 mg/kg/dose q24h
:::::::::: If Serum creatinine 1–1.2 then [[Vancomycin]] IV 15 mg/kg/dose q24h
:::::::::: If Serum creatinine 1.3–1.6 then  [[Vancomycin]] IV 10 mg/kg/dose q24h
:::::::::: If Serum creatinine >1.6 15 then [[Vancomycin]] IV mg/kg/dose q48h
::::::::::: Note : Begin treatment with a 20-mg/kg loading dose {{or}}
:::::::: (b). Alternatives for penicillin-susceptible strains
:::::::::* (a) For 32–34 weeks gestational age
:::::::::: For 0–1 week of Age : [[Penicillin G]] IV 200000 U/kg/day,divided q12h, {{or}} [[Ampicillin]] IV 100 mg/kg/day,divided q12h
:::::::::: For 1–4 week of Age : [[Penicillin G]] IV 300000 U/kg/day,divided q8h, {{or}} [[Ampicillin]] IV 150 mg/kg/day,divided q8h
:::::::::* (b) For 34–37 week gestational age
:::::::::: For 0–1 week of Age : [[Penicillin G]] IV 300000 U/kg/day,divided q8h, {{or}}  [[Ampicillin]] IV 150 mg/kg/day,divided q8h
:::::::::: For 1–4 week of Age : [[Penicillin G]] IV 400000 U/kg/day,divided q6h, {{or}} [[Ampicillin]] IV 200 mg/kg/day,divided q6h
:::::::::* (c) Term Newborn Infant
:::::::::: For 0–1 week of Age : [[Penicillin G]] IV 300000 U/kg/day,divided q8h, {{or}} [[Ampicillin]] IV 150 mg/kg/day,divided q8h
:::::::::: For 1–4 week of Age : [[Penicillin G]] IV 400000 U/kg/day,divided q6h, {{or}} [[Ampicillin]] IV 200 mg/kg/day,divided q6h {{and}}
 
::::::*(2).'''A protein synthesis inhibitor'''
:::::::* (a) For 32–34 weeks gestational age
:::::::: For 0–1 week of Age : [[Clindamycin]] IV 10 mg/kg/day, divided q12h, {{or}} [[Linezolid]] IV 20 mg/kg/day, divided q12h, {{or}} [[Rifampin]] IV 10 mg/kg/day, q24h
:::::::: For 1–4 week of Age : [[Clindamycin]] IV 15 mg/kg/day, divided q8h, {{or}}  [[Linezolid]] IV 30 mg/kg/day, divided q8h, {{or}}  [[Rifampin]] IV 10 mg/kg/day, q24h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 week of Age : [[Clindamycin]] IV 15 mg/kg/day, divided q8h, {{or}} [[Linezolid]] IV 30 mg/kg/day, divided q8h, {{or}}  [[Rifampin]] IV 10 mg/kg/day, q24h
:::::::: For 1–4 week of Age : [[Clindamycin]] IV 20 mg/kg/day, divided q6h, {{or}} [[Linezolid]] IV 30 mg/kg/day, divided q8h, {{or}}  [[Rifampin]] IV 10 mg/kg/day, q24h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : [[Clindamycin]] IV 15 mg/kg/day, divided q8h, {{or}}  [[Linezolid]] IV 30 mg/kg/day, divided q8h, {{or}} [[Doxycycline]] IV 4.4 mg/kg/day, divided q12h, (loading dose 4.4 mg/kg)  {{or}} [[Rifampin]] IV 10 mg/kg/day, q24h
:::::::: For 1–4 week of Age : [[Clindamycin]] IV 20 mg/kg/day, divided q6h, {{or}} [[Linezolid]] IV 30 mg/kg/day, divided q8h, {{or}} [[Doxycycline]] IV 4.4 mg/kg/day, divided q12h, (loading dose 4.4 mg/kg)  {{or}} [[Rifampin]] IV 10 mg/kg/day, q24h
::::::::: Note: Duration of therapy: For ≥2–3 wk, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness


:::::*(C). Oral follow-up combination therapy for severe anthrax
== Historical background ==
::::::(1).'''A bactericidal antimicrobial'''
French physician [[Casimir Davaine]] (1812-1882) demonstrated the symptoms of anthrax were invariably accompanied by the microbe ''B. anthracis''.<ref>{{cite journal
::::::: (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
|last=Théodoridès
::::::::* (a) For 32–34 weeks gestational age
|first=J
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] PO 20 mg/kg/day, divided q12h'''
|authorlink=
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] PO 20 mg/kg/day, divided q12h'''
|date=April 1966
::::::::* (b) For 34–37 week gestational age
|title=Casimir Davaine (1812-1882): a precursor of Pasteur
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] PO 20 mg/kg/day, divided q12h'''
|journal=Medical history
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] PO 20 mg/kg/day, divided q12h'''
|volume=10
::::::::* (c) Term Newborn Infant
|issue=2
::::::::: For 0–1 week of Age : '''[[Ciprofloxacin]] PO 30 mg/kg/day, divided q12h'''
|pages=155–65
::::::::: For 1–4 week of Age : '''[[Ciprofloxacin]] PO 30 mg/kg/day, divided q12h''' {{or}}
| publisher = | pmid = 5325873
:::::::(b). Alternatives for penicillin-susceptible strains
| bibcode = |pmc=1033586
::::::::* (a) For 32–34 weeks gestational age
| doi=10.1017/S0025727300010942
::::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 50 mg/kg/day, divided q12h, {{or}} Penicillin VK PO 50 mg/kg/day, divided q12h
}}</ref>  German physician [[Aloys Pollender]] (1799–1879) is also credited for this discovery. ''B. anthracis'' was the first bacterium conclusively demonstrated to cause disease, by [[Robert Koch]] in 1876.<ref>Koch, R. (1876) "Untersuchungen über Bakterien: V. Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des ''Bacillus anthracis''" (Investigations into bacteria: V. The etiology of anthrax, based on the ontogenesis of ''Bacillus anthracis''), Cohns ''Beitrage zur Biologie der Pflanzen'', vol. 2, no. 2, [http://edoc.rki.de/documents/rk/508-5-26/PDF/5-26.pdf pages 277–310].</ref> The species name ''anthracis'' is from the [[Greek language|Greek]] ''anthrax''<!--[sic]--> (ἄνθραξ), meaning "coal" and referring to the most common form of the disease, [[cutaneous]] anthrax, in which large, black skin [[lesion]]s are formed.
::::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin VK PO 75 mg/kg/day, divided q8h
::::::::* (b) For 34–37 week gestational age
::::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 50 mg/kg/day, divided q12h {{or}} Penicillin VK PO  50 mg/kg/day, divided q12h
::::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin VK PO 75 mg/kg/day, divided q8h
::::::::* (c) Term Newborn Infant
::::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin VK PO 75 mg/kg/day, divided q8h
::::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin VK PO 75 mg/kg/day, divided q6–8h  {{and}}
::::::(2).'''A protein synthesis inhibitor'''
:::::::* (a) For 32–34 weeks gestational age
:::::::: For 0–1 week of Age : '''[[Clindamycin]] PO 10 mg/kg/day, divided q12h''' {{or}} [[Linezolid]] PO 20 mg/kg/day, divided q12h
:::::::: For 1–4 week of Age : '''[[Clindamycin]] PO 15 mg/kg/day, divided q8h''' {{or}} [[Linezolid]] PO 30 mg/kg/day, divided q8h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 week of Age : '''[[Clindamycin]] PO 15 mg/kg/day, divided q8h''' {{or}} [[Linezolid]] PO 30 mg/kg/day, divided q8h
:::::::: For 1–4 week of Age : '''[[Clindamycin]] PO 20 mg/kg/day, divided q6h''' {{or}} [[Linezolid]] PO 30 mg/kg/day, divided q8h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : '''[[Clindamycin]] PO 15 mg/kg/day, divided q8h''' {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (loading dose 4.4 mg/kg) {{or}} [[Linezolid]] PO 30 mg/kg/day, divided q8h
:::::::: For 1–4 week of Age :'''[[Clindamycin]] PO 20 mg/kg/day, divided q6h''' {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (loading dose 4.4 mg/kg) {{or}} [[Linezolid]] PO 30 mg/kg/day, divided q8h  {{or}}
::::::::: Note: Duration of therapy: to complete a treatment course of 10–14 days or greater. May require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness.


:::::*(D).Treatment of cutaneous anthrax without systemic involvement
==Biology==
::::::*(1).'''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
[[B. anthracis]], the causative agent of [[anthrax]], is a [[motility|nonmotile]], [[Gram-positive]], [[aerobic]] or facultatively [[anaerobic]], [[endospore]]-forming, [[rod]]-shaped [[bacterium]] approximately 4 μm by 1 μm, although under the microscope it frequently appears in chains of [[cells]]. Like other [[Bacillus]], [[Bacillus anthracis]] is saprophyte, being able to live in vegetation, air, water and soil.<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>
:::::::* (a) For 32–34 weeks gestational age
:::::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 10 mg/kg/day, divided q12h
:::::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
:::::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 20 mg/kg/day, divided q6h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 30 mg/kg/day, divided q12h {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (Loading dose 4.4 mg/kg) {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
:::::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 30 mg/kg/day, divided q12h {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (Loading dose 4.4 mg/kg) {{or}} [[Clindamycin]] PO 20 mg/kg/day, divided q6h
::::::*(2).'''Alternatives for penicillin-susceptible strains'''
:::::::* (a) For 32–34 weeks gestational age
:::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 50 mg/kg/day, divided q12h {{or}} Penicillin Vk PO 50 mg/kg/day, divided q12h
:::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin Vk PO 75 mg/kg/day, divided q8h
:::::::* (b) For 34–37 week gestational age
:::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 50 mg/kg/day, divided q12h {{or}} Penicillin Vk PO 50 mg/kg/day, divided q12h
:::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin Vk PO 75 mg/kg/day, divided q8h
:::::::* (c) Term Newborn Infant
:::::::: For 0–1 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin Vk PO 75 mg/kg/day, divided q8h
:::::::: For 1–4 week of Age : '''[[Amoxicillin]]''' PO 75 mg/kg/day, divided q8h {{or}} Penicillin Vk PO 75 mg/kg/day, divided q6–8h
::::::::: Note : Duration of therapy for naturally acquired infection is 7–10 days and for a biological weapon–related event,may require additional prophylaxis for inhaled spores to complete an antimicrobial course of up to 60 days from onset of illness.


:* [[Bacillus anthracis]], postexposure prophylaxis
These [[bacterial]] [[cells]] may occur isolated, form groups of 2 or more [[cells]] in the body, or long chains in [[cell culture|cultures]].<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref> In [[blood smear]]s, smears of [[tissue]]s or lesion fluid from [[diagnostic]] specimens, these chains are two to a few [[cells]] in length. In smears made from [[in vitro]] cultures, they can appear as endless strings of [[cells]] - responsible for the characteristic tackiness of the colonies and for the flocculating nature of broth cultures. [[Cell culture]]s appear with a large, grey and curled structure, resembling a "medusa head".<ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>
::* '''For adults'''<ref name="pmid24447897">{{cite journal| author=Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT et al.| title=Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. | journal=Emerg Infect Dis | year= 2014 | volume= 20 | issue= 2 | pages= | pmid=24447897 | doi=10.3201/eid2002.130687 | pmc=PMC3901462 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24447897  }} </ref>
:::* (1) For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: '''[[Ciprofloxacin]], 500 mg q12h''' {{or}} '''Doxycycline, 100 mg q12h''' {{or}} Levofloxacin, 750 mg q24h {{or}} Moxifloxacin, 400 mg q24h {{or}} Clindamycin, 600 mg q8h {{or}}
:::* (2) Alternatives for penicillin-susceptible strain Amoxicillin, 1 g q8h {{or}} Penicillin VK, 500 mg q6h
:::: Note (1): Preferred drugs are indicated in boldface.
:::: Note (2): Alternative drugs are listed in order of preference for treatment for patients who cannot take first-line treatment or if first-line treatment is unavailable.


::* '''For children ≥ 1 month'''<ref name="pmid24777226">{{cite journal| author=Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D et al.| title=Pediatric anthrax clinical management. | journal=Pediatrics | year= 2014 | volume= 133 | issue= 5 | pages= e1411-36 | pmid=24777226 | doi=10.1542/peds.2014-0563 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24777226 }} </ref>
[[B. anthracis]] have a characteristic square-ended appearance, traditionally associated with its vegetative state, although this may not always be very clear. In the presence of [[oxygen]], ideally at 32 - 35 ºC, and towards the end of the exponential phase of growth, one ellipsoidal [[spore]] (approximately 2 μm by 1 μm in size) is formed within each [[cell]].<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref> Commonly the [[spores]] will be produced once the [[cell]] senses scarcity of [[nutrients]].<ref name="pmid12610093">{{cite journal| author=Spencer RC| title=Bacillus anthracis. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 3 | pages= 182-7 | pmid=12610093 | doi= | pmc=PMC1769905 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12610093 }} </ref>
:::* (1) For penicillin-resistant strains or prior to susceptibility testing: '''[[Ciprofloxacin]], 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose)''' {{or}} '''[[Doxycycline]], <45 kg: 4.4 mg/kg/day, PO, divided q12h (not to exceed 100 mg/dose)''' >45 kg: 100 mg/dose, PO, given q12h {{or}} [[Clindamycin]], 30 mg/kg/day, PO, divided q8h (not to exceed 900 mg/dose) {{or}} [[Levofloxacin]], <50 kg: 16 mg/kg/day, PO, divided q12h (not to exceed 250 mg/dose) >50 kg: 500 mg, PO, given q24h {{or}}
:::* (2) For penicillin-susceptible strains: '''[[Amoxicillin]], 75 mg/kg/day, PO, divided every q8h (not to exceed 1 g/dose)''' {{or}} [[Penicillin VK]], 50-75 mg/kg/day, PO, divided q6h to q8h
:::: Note (1) : '''Duration of Therapy is 60 days after exposure'''
:::: Note (2) : Bold font are  preferred antimicrobial agent (when 2 bolded antimicrobial agents are present, both are considered equivalent in overall safety and efficacy).
:::: Note (3) : Normal font are alternative selections are listed in order of preference for therapy for patients who cannot take first-line therapy or if first-line therapy is unavailable.
:::: Note (4) : Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.
:::: Note (5) : Italicized font: indicates FDA approval for the indication in the pediatric population.
:::: Note (6) : A single 14-day course of doxycycline is not routinely associated with tooth staining, but some degree of staining is likely for a prolonged treatment course of up to 60 days.
:::: Note (7) : Safety data for [[Levofloxacin]] in the pediatric population are limited to 14 days for duration therapy.
:::: Note (8) : Be aware of the possibility of emergence of penicillin-resistance during monotherapy with [[Amoxicillin]] or [[Penicillin]].


::* '''For children < 1 month'''
The [[spores]] of [[B. anthracis]], which can remain dormant in the environment for decades, being resistant to heat and disinfectants, are the [[infectious]] form, but vegetative [[B. anthracis]] rarely causes disease.<ref>{{Cite journal | author = [[Sean V. Shadomy]] & [[Theresa L. Smith]] | title = Zoonosis update. Anthrax | journal = [[Journal of the American Veterinary Medical Association]] | volume = 233 | issue = 1 | pages = 63–72 | year = 2008 | month = July | doi = 10.2460/javma.233.1.63 | pmid = 18593313}}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref>
:::* (1) '''For all strains, regardless of penicillin susceptibility or if susceptibility is unknown'''
::::* (a) For 32–34 weeks gestational age
::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 10 mg/kg/day, divided q12h
::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
::::* (b) For 34–37 week gestational age
::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 20 mg/kg/day, divided q12h {{or}} [[Clindamycin]] PO 20 mg/kg/day, divided q6h
::::* (c) Term Newborn Infant
::::: For 0–1 week of Age : '''[[Ciprofloxacin]]''' PO 30 mg/kg/day, divided q12h {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (Loading dose 4.4 mg/kg) {{or}} [[Clindamycin]] PO 15 mg/kg/day, divided q8h
::::: For 1–4 week of Age : '''[[Ciprofloxacin]]''' PO 30 mg/kg/day, divided q12h {{or}} [[Doxycycline]] PO 4.4 mg/kg/day, divided q12h (Loading dose 4.4 mg/kg) {{or}} [[Clindamycin]] PO 20 mg/kg/day, divided q6h  {{or}}
:::* (2) '''Alternatives for penicillin-susceptible strains'''
::::* (a) For 32–34 weeks gestational age
::::: For 0–1 week of Age : [[Amoxicillin]] PO 50 mg/kg/day, divided q12h {{or}} [[Penicillin Vk]] PO 50 mg/kg/day, divided q12h
::::: For 1–4 week of Age : [[Amoxicillin]] PO 75 mg/kg/day, divided q8h {{or}} [[Penicillin Vk]] PO 75 mg/kg/day, divided q8h
::::* (b) For 34–37 week gestational age
:::::: For 0–1 week of Age : [[Amoxicillin]] PO 50 mg/kg/day, divided q12h {{or}} [[Penicillin Vk]] PO 50 mg/kg/day, divided q12h
:::::: For 1–4 week of Age : [[Amoxicillin]] PO 75 mg/kg/day, divided q8h {{or}} [[Penicillin Vk]] PO 75 mg/kg/day, divided q8h
::::* (c) Term Newborn Infant
::::: For 0–1 week of Age : [[Amoxicillin]] PO 75 mg/kg/day, divided q8h {{or}} [[Penicillin Vk]] PO 75 mg/kg/day, divided q8h
::::: For 1–4 week of Age : [[Amoxicillin]] PO 75 mg/kg/day, divided q8h {{or}} [[Penicillin Vk]] PO 75 mg/kg/day, divided q6–8h
::::: Note: Duration of therapy is  60 days from exposure


==Gallery==
In the absence of [[oxygen]] and under a high partial pressure of Co2, in the presence of [[bicarbonate]], the vegetative [[cell]] secretes its [[polypeptide]] [[capsule]]. This is one of the two established [[in vivo]] [[virulence factor]]s of [[B. anthracis]]. The [[capsule]] is also a primary [[diagnostic]] aid.<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref> Protective [[antigen]] (PA) and [[edema]] factor (EF) combine to form [[edema]] toxin (ET) and PA and lethal factor (LF) combine to form lethal toxin (LT), the active [[toxins]].<ref>{{Cite journal | author = [[Mahtab Moayeri]] & [[Stephen H. Leppla]] | title = The roles of anthrax toxin in pathogenesis | journal = [[Current opinion in microbiology]] | volume = 7 | issue = 1 | pages = 19–24 | year = 2004 | month = February | doi = 10.1016/j.mib.2003.12.001 | pmid = 15036135}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>


<gallery>


Image: Bacillus_anthracis01.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
{| style="float: right;"
| [[File:AnthraxCauses2.png|200px|thumb|none| Photomicrograph depicting a number of Gram-positive, endospore-forming Bacillus anthracis bacteria<SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|-
| [[File:AnthraxCauses1.jpg|200px|thumb|none| Scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteria<SMALL>Courtesy: ''[http://phil.cdc.gov/phil/home.asp Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
|}


Image: Bacillus_anthracis02.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Genome structure==
''B. anthracis'' has a single chromosome which is a circular, 5,227,293-bp DNA molecule.<ref name="Read">{{cite journal|last=Read|first=TD|coauthors=Peterson, SN; Tourasse, N; Baillie, LW; Paulsen, IT; Nelson, KE; Tettelin, H; Fouts, DE; Eisen, JA; Gill, SR; Holtzapple, EK; Okstad, OA; Helgason, E; Rilstone, J; Wu, M; Kolonay, JF; Beanan, MJ; Dodson, RJ; Brinkac, LM; Gwinn, M; DeBoy, RT; Madpu, R; Daugherty, SC; Durkin, AS; Haft, DH; Nelson, WC; Peterson, JD; Pop, M; Khouri, HM; Radune, D; Benton, JL; Mahamoud, Y; Jiang, L; Hance, IR; Weidman, JF; Berry, KJ; Plaut, RD; Wolf, AM; Watkins, KL; Nierman, WC; Hazen, A; Cline, R; Redmond, C; Thwaite, JE; White, O; Salzberg, SL; Thomason, B; Friedlander, AM; Koehler, TM; Hanna, PC; Kolstø, AB; Fraser, CM|title=The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria.|journal=Nature|date=May 1, 2003|volume=423|issue=6935|pages=81–6|pmid=12721629|doi=10.1038/nature01586}}</ref>  It also has two circular, extrachromosomal, double-stranded DNA plasmids, pXO1 and pXO2. Both the pXO1 and pXO2 plasmids are required for full virulence and represent two distinct plasmid families.<ref name="Kolstø">{{cite journal|last=Kolstø|first=Anne-Brit|author2=Tourasse, Nicolas J.|author3= Økstad, Ole Andreas|title=What Sets                            Apart from Other                            Species?|journal=Annual Review of Microbiology|date=1 October 2009|volume=63|issue=1|pages=451–476|doi=10.1146/annurev.micro.091208.073255}}</ref>


Image: Bacillus_anthracis03.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
{| class="wikitable"
|-
! Feature !! scope="col" width="100px" | Chromosome !! scope="col" width="100px" | pXO1 !! scope="col" width="100px" | pXO2
|-
| Size (bp) || align="right"|5,227,293 || align="right"|181,677 || align="right"|94,829
|-
| Number of genes || align="right"|5,508 || align="right"|217 || align="right"|113
|-
| [[Replicon (genetics)|Replicon]] coding (%) || align="right"|84.3 || align="right"|77.1 || align="right"|76.2
|-
| Average [[gene]] length (nt) || align="right"|800 || align="right"|645 || align="right"|639
|-
| G+C content (%) || align="right"|35.4 || align="right"|32.5 || align="right"|33.0
|-
| [[rRNA]] operons || align="right"|11 || align="right"|0 || align="right"|0
|-
| [[tRNA]]s || align="right"|95 || align="right"|0 || align="right"|0
|-
| [[Small RNA|sRNAs]] || align="right"|3 || align="right"|2 || align="right"|0
|-
| [[Phage]] genes || align="right"|62 || align="right"|0 || align="right"|0
|-
| [[Transposon]] genes || align="right"|18 || align="right"|15 || align="right"|6
|-
| Disrupted reading frame || align="right"|37 || align="right"|5 || align="right"|7
|-
| Genes with assigned function || align="right"|2,762 || align="right"|65 || align="right"|38
|-
| Conserved hypothetical genes || align="right"|1,212 || align="right"|22 || align="right"|19
|-
| Genes of unknown function || align="right"|657 || align="right"|8 || align="right"|5
|-
| Hypothetical genes || align="right"|877 || align="right"|122 || align="right"|51
|}


Image: Bacillus_anthracis05.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
===pXO1 plasmid===
The pXO1 plasmid (182 kb) contains the genes that encode for the [[anthrax toxin]] components: ''pag'' (protective antigen, PA), ''lef'' (lethal factor, LF), and ''cya'' (edema factor, EF). These factors are contained within a 44.8-kb [[pathogenicity island]] (PAI). The lethal toxin is a combination of PA with LF and the edema toxin is a combination of PA with EF. The PAI also contains genes which encode a [[transcriptional activator]] AtxA and the [[repressor]] PagR, both of which regulate the expression of the anthrax toxin genes.<ref name="Kolstø" />


Image: Bacillus_anthracis06.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
===pXO2 plasmid===
pXO2 encodes a five-gene [[operon]] (''capBCADE'') which synthesizes a poly-γ-D-glutamic acid (polyglutamate) capsule.  This capsule allows ''B. anthracis'' to evade the host immune system by protecting itself from [[phagocytosis]]. Expression of the capsule operon is activated by the transcriptional regulators AcpA and AcpB, located in the pXO2 pathogenicity island (35 kb). Interestingly, AcpA and AcpB expression are under the control of AtxA from pXO1.<ref name="Kolstø" />


Image: Bacillus_anthracis07.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Strains==
The 89 known strains of ''B. anthracis'' include:
*[[Sterne strain]] (34F2; aka the "Weybridge strain"), used by [[Max Sterne]] in his 1930s vaccines
*[[Vollum strain]], formerly weaponized by the US, UK, and Iraq; isolated from cow in [[Oxfordshire]], UK, in 1935
**Vollum M-36, virulent British research strain; passed through macaques 36 times
**Vollum 1B, weaponized by the US and UK in the 1940s-60s
**Vollum-14578, UK biotesting contaminated [[Gruinard Island]], Scotland, in 1940s
**V770-NP1-R, the avirulent, nonencapsulated strain used in the ''[[BioThrax]]'' vaccine
*Anthrax 836, highly virulent strain weaponized by the USSR; discovered in [[Kirov, Kirov Oblast|Kirov]] in 1953
*[[Ames strain]], isolated from a cow in [[Texas]] in 1981; famously used in [[AMERITHRAX]] letter attacks (2001)
**Ames Ancestor
**Ames Florida
*H9401, isolated from human patient in Korea; used in investigational anthrax vaccines<ref name="Chun" />


Image: Bacillus_anthracis08.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Evolution==
Whole genome sequencing has made reconstruction of the ''B. anthracis'' phylogeny extremely accurate. A contributing factor to the reconstruction is ''B. anthracis'' being monomorphic, meaning it has low genetic diversity, including the absence of any measurable lateral DNA transfer since its derivation as a species. The lack of diversity is due to a short evolutionary history that has precluded mutational saturation in [[single nucleotide polymorphisms]].<ref name="Keim">{{cite journal|last=Keim|first=Paul|author2=Gruendike, Jeffrey M.|author3= Klevytska, Alexandra M.|author4= Schupp, James M.|author5= Challacombe, Jean|author6= Okinaka, Richard|title=The genome and variation of Bacillus anthracis|journal=Molecular Aspects of Medicine|date=1 December 2009|volume=30|issue=6|pages=397–405|doi=10.1016/j.mam.2009.08.005|pmid=19729033|pmc=3034159}}</ref>


Image: Bacillus_anthracis09.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
A short evolutionary time does not necessarily mean a short chronological time. When DNA is replicated, mistakes occur which become genetic mutations.  The buildup of these mutations over time leads to the evolution of a species. During the ''B. anthracis'' lifecycle, it spends a significant amount of time in the soil spore reservoir stage, a stage in which DNA replication does not occur. These prolonged periods of dormancy have greatly reduced the evolutionary rate of the organism.<ref name="Keim" />


Image: Bacillus_anthracis10.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
===Nearest neighbors===
''B. anthracis'' belongs to the ''B. cereus'' group consisting of the strains: ''B. cereus'', ''B. anthracis'', ''B. thuringiensis'', ''[[Bacillus weihenstephanensis|B. weihenstephanensis]]'', ''[[Bacillus mycoides|B. mycoides]]'', and ''B. pseudomycoides''.  The first three strains are pathogenic or opportunistic to insects or mammals, while the last three are not considered pathogenic.  The strains of this group are genetically and phenotypically heterogeneous overall, but some of the strains are more closely related and phylogenetically intermixed at the chromosome level. The ''B. cereus'' group generally exhibits complex genomes and most carry varying numbers of plasmids.<ref name="Kolstø" />


Image: Bacillus_anthracis11.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
''B. cereus'' is a soil-dwelling bacterium which can colonize the gut of invertebrates as a symbiont<ref>{{cite journal|last=Jensen|first=G. B.|author2=Hansen, B. M.|author3= Eilenberg, J.|author4= Mahillon, J.|title=The hidden lifestyles of Bacillus cereus and relatives|journal=Environmental Microbiology|date=18 July 2003|volume=5|issue=8|pages=631–640|doi=10.1046/j.1462-2920.2003.00461.x|pmid=12871230}}</ref>   and is a frequent cause of food poisoning<ref>{{cite journal|last=Drobniewski|first=FA|title=Bacillus cereus and related species.|journal=Clinical Microbiology Reviews|date=October 1993|volume=6|issue=4|pages=324–38|pmid=8269390|pmc=358292}}</ref>  It produces an emetic toxin, enterotoxins, and other virulence factors.<ref>{{cite journal|last=Stenfors Arnesen|first=Lotte P.|author2=Fagerlund, Annette|author3= Granum, Per Einar|title=From soil to gut:                            and its food poisoning toxins|journal=FEMS Microbiology Reviews|date=1 July 2008|volume=32|issue=4|pages=579–606|doi=10.1111/j.1574-6976.2008.00112.x|pmid=18422617}}</ref>   The enterotoxins and virulence factors are encoded on the chromosome, while the emetic toxin is encoded on a 270-kb plasmid, pCER270.<ref name="Kolstø" />


Image: Bacillus_anthracis12.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
''B. thuringiensis'' is an insect pathogen and is characterized by production of parasporal crystals of insecticidal toxins Cry and Cyt.<ref>{{cite journal|last=Schnepf|first=E|author2=Crickmore, N|author3=Van Rie, J|author4=Lereclus, D|author5=Baum, J|author6=Feitelson, J|author7=Zeigler, DR|author8= Dean, DH|title=Bacillus thuringiensis and its pesticidal crystal proteins.|journal=Microbiology and molecular biology reviews : MMBR|date=September 1998|volume=62|issue=3|pages=775–806|pmid=9729609|pmc=98934}}</ref>   The genes encoding these proteins are commonly located on plasmids which can be lost from the organism, making it indistinguishable from ''B. cereus''.<ref name="Kolstø" />


Image: Bacillus_anthracis13.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
===Pseudogene===
''PlcR'' is a global transcriptional regulator which controls most of the secreted virulence factors in ''B. cereus'' and ''B. thuringiensis''.  It is chromosomally encoded and is ubiquitous throughout the cell.<ref>{{cite journal|last=Agaisse|first=H|author2=Gominet, M|author3= Okstad, OA|author4= Kolstø, AB|author5= Lereclus, D|title=PlcR is a pleiotropic regulator of extracellular virulence factor gene expression in Bacillus thuringiensis.|journal=Molecular microbiology|date=June 1999|volume=32|issue=5|pages=1043–53|pmid=10361306|doi=10.1046/j.1365-2958.1999.01419.x}}</ref>   In ''B. anthracis'', however, the ''plcR'' gene contains a single base change at position 640, a nonsense mutation, which creates a dysfunctional protein. While 1% of the ''B. cereus'' group carries an inactivated ''plcR'' gene, none of them carries the specific mutation found only in ''B. anthracis''.<ref>{{cite journal|last=Slamti|first=L|author2=Perchat, S|author3=Gominet, M|author4=Vilas-Bôas, G|author5=Fouet, A|author6=Mock, M|author7=Sanchis, V|author8=Chaufaux, J|author9=Gohar, M|author10= Lereclus, D|title=Distinct mutations in PlcR explain why some strains of the Bacillus cereus group are nonhemolytic.|journal=Journal of bacteriology|date=June 2004|volume=186|issue=11|pages=3531–8|pmid=15150241|doi=10.1128/JB.186.11.3531-3538.2004|pmc=415780}}</ref>


Image: Bacillus_anthracis14.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
The ''plcR'' gene is part of a two-gene operon with ''papR''.<ref>{{cite journal|last=Okstad|first=OA|author2=Gominet, M|author3= Purnelle, B|author4= Rose, M|author5= Lereclus, D|author6= Kolstø, AB|title=Sequence analysis of three Bacillus cereus loci carrying PIcR-regulated genes encoding degradative enzymes and enterotoxin.|journal=Microbiology (Reading, England)|date=November 1999|volume=145|pages=3129–38|pmid=10589720|issue=11}}</ref><ref name="Slamti">{{cite journal|last=Slamti|first=L|author2=Lereclus, D|title=A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group.|journal=The EMBO Journal|date=Sep 2, 2002|volume=21|issue=17|pages=4550–9|pmid=12198157|pmc=126190|doi=10.1093/emboj/cdf450}}</ref>  The ''papR'' gene encodes a small protein which is secreted from the cell and the reimported as a processed heptapeptide forming a quorum-sensing system.<ref name="Slamti" /><ref>{{cite journal|last=Bouillaut|first=L|author2=Perchat, S|author3=Arold, S|author4=Zorrilla, S|author5=Slamti, L|author6=Henry, C|author7=Gohar, M|author8=Declerck, N|author9= Lereclus, D|title=Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides|journal=Nucleic Acids Research|date=June 2008|volume=36|issue=11|pages=3791–801|pmid=18492723|doi=10.1093/nar/gkn149|pmc=2441798}}</ref> The lack of PlcR in ''B. anthracis'' is a principle characteristic differentiating it from other members of the ''B. cereus'' group.  While ''B. cereus'' and ''B. thuringiensis'' depend on the ''plcR'' gene for expression of their virulence factors, ''B. anthracis'' relies on the pXO1 and pXO2 plasmids for its virulence.<ref name="Kolstø" />


Image: Bacillus_anthracis15.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
== Laboratory research ==
Components of [[tea]], such as [[polyphenols in tea|polyphenol]]s, have the ability to inhibit the activity both of ''B. anthracis'' and its toxin considerably; spores, however, are not affected. The addition of milk to the tea completely inhibits its antibacterial activity against anthrax.<ref>{{cite web|url = http://web.archive.org/web/20090213231226/http://www.sfam.org.uk/newsarticle.php?214&2 |title=Anthrax and tea|publisher = Society for Applied Microbiology |accessdate = 2011-12-21|date=2011-12-21}}</ref> Activity against the ''B. athracis'' in the [[laboratory]] does not prove that drinking tea affects the course of an infection, since it is unknown how these polyphenols are absorbed and distributed within the body.


Image: Bacillus_anthracis16.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
===Recent research===
Advances in genotyping methods have led to improved genetic analysis for variation and relatedness. These methods include multiple-locus variable-number tandem repeat analysis ([[MLVA]]) and typing systems using canonical [[single-nucleotide polymorphisms]]. The Ames ancestor chromosome was sequenced in 2003<ref name="Read" /> and contributes to the identification of genes involved in the virulence of ''B. anthracis''. Recently, ''B. anthracis'' isolate H9401 was isolated from a Korean patient suffering from gastrointestinal anthrax.  The goal of the Republic of Korea is to use this strain as a challenge strain to develop a recombinant vaccine against anthrax.<ref name="Chun">{{cite journal|last=Chun|first=J.-H.|author2=Hong, K.-J.|author3=Cha, S. H.|author4=Cho, M.-H.|author5=Lee, K. J.|author6=Jeong, D. H.|author7=Yoo, C.-K.|author8= Rhie, G.-e.|title=Complete Genome Sequence of Bacillus anthracis H9401, an Isolate from a Korean Patient with Anthrax|journal=Journal of Bacteriology|date=18 July 2012|volume=194|issue=15|pages=4116–4117|doi=10.1128/JB.00159-12|pmid=22815438|pmc=3416559}}</ref>


Image: Bacillus_anthracis17.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
The H9401 strain isolated in the Republic of Korea was sequenced using [[454 Life Sciences|454]] GS-FLX technology and analyzed using several bioinformatics tools to align, annotate, and compare H9401 to other ''B. anthracis'' strains.  The sequencing coverage level suggests a molecular ratio of pXO1:pXO2:chromosome as 3:2:1 which is identical to the Ames Florida and Ames Ancestor strains. H9401 has 99.679% sequence homology with Ames Ancestor with an [[amino acid]] sequence homology of 99.870%. H9401 has a circular chromosome (5,218,947 bp with 5,480 predicted [[Open reading frame|ORF]]s), the pXO1 plasmid (181,700 bp with 202 predicted ORFs), and the pXO2 plasmid (94,824 bp with 110 predicted ORFs).<ref name="Chun" /> As compared to the Ames Ancestor chromosome above, the H9401 chromosome is about 8.5 kb smaller. Due to the high pathogenecity and sequence similarity to the Ames Ancestor, H9401 will be used as a reference for testing the efficacy of candidate anthrax vaccines by the Repbulic of Korea.<ref name="Chun" />


Image: Bacillus_anthracis18.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
== Host interactions ==
As with most other pathogenic bacteria, ''B. anthracis'' must acquire iron to grow and proliferate in its host environment. The most readily available iron sources for pathogenic bacteria are the [[heme]] groups used by the host in the transport of oxygen. To scavenge heme from host [[hemoglobin]] and [[myoglobin]], ''B. anthracis'' uses two secretory [[siderophore]] proteins, IsdX1 and IsdX2. These proteins can separate heme from hemoglobin, allowing surface proteins of ''B. anthracis'' to transport it into the cell.<ref>{{cite journal |author = Maresso AW, Garufi G, Schneewind O |title=Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from Hemoglobin |journal= PLOS Pathogens |volume=4(8): e1000132|year=2008}}</ref>


Image: Bacillus_anthracis19.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Origin==
[[Bacillus anthracis]] is thought to have originated in Egypt and Mesopotamia. Many scholars think that in Moses’ time, during the 10 plagues of Egypt, [[anthrax]] may have caused what was known as the fifth [[plague]], described as a sickness affecting horses, cattle, sheep, camels and oxen.


Image: Bacillus_anthracis20.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Tropism==
After entering the body (through the [[skin]], [[lungs]], [[gastrointestinal tract]] or by [[injection]]), [[B. anthracis]] [[spores]] are believed to germinate locally or be transported by [[phagocytic cells]] to the [[lymphatics]] and regional [[lymph nodes]], where they germinate.<ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref><ref name="Ross1957">{{cite journal|last1=Ross|first1=Joan M.|title=The pathogenesis of anthrax following the administration of spores by the respiratory route|journal=The Journal of Pathology and Bacteriology|volume=73|issue=2|year=1957|pages=485–494|issn=0368-3494|doi=10.1002/path.1700730219}}</ref> After binding to [[cell]] surface receptors, the PA portion of the complexes facilitates translocation of the [[toxins]] to the [[cytosol]].<ref name="Moayeri2004">{{cite journal|last1=Moayeri|first1=M|title=The roles of anthrax toxin in pathogenesis|journal=Current Opinion in Microbiology|volume=7|issue=1|year=2004|pages=19–24|issn=13695274|doi=10.1016/j.mib.2003.12.001}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>


Image: Bacillus_anthracis21.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Natural Reservoir==
[[Natural reservoir]]s of [[Bacillus anthracis]] include:<ref name=WHO>{{cite web | title = Anthrax in Humans and Animals | url = http://www.who.int/csr/resources/publications/anthrax_web.pdf }}</ref><ref name="BhatnagarBatra2001">{{cite journal|last1=Bhatnagar|first1=Rakesh|last2=Batra|first2=Smriti|title=Anthrax Toxin|journal=Critical Reviews in Microbiology|volume=27|issue=3|year=2001|pages=167–200|issn=1040-841X|doi=10.1080/20014091096738}}</ref><ref name=CDC>{{cite web | title = Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults | url = http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article }}</ref>
* Humans
* Mammals
* Herbivores
* Reptiles
* Birds


Image: Bacillus_anthracis22.jpeg| Bacillus anthracis. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


</gallery>
== References ==
{{Reflist|2}}


==References==
== External links ==
<!-- ---------------------------------------------------------------
{{commons category|Bacillus anthracis}}
See http://en.wikipedia.org/wiki/Wikipedia:Footnotes for a
* [http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=1392 Bacillus anthracis] genomes and related information at [http://patricbrc.org/ PATRIC], a Bioinformatics Resource Center funded by [http://www.niaid.nih.gov/ NIAID]
discussion of different citation methods and how to generate
* [http://hazard.hegroup.org/query/query_detail.php?c_hazard_ID=64 Hazards in Animal Research Database - ''Bacillus anthracis'']
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* [http://pathema.jcvi.org/cgi-bin/Bacillus/PathemaHomePage.cgi Pathema-''Bacillus'' Resource]
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Latest revision as of 15:40, 21 August 2015

style="background:#Template:Taxobox colour;"|Bacillus anthracis
Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain)
Photomicrograph of Bacillus anthracis (fuchsin-methylene blue spore stain)
style="background:#Template:Taxobox colour;" | Scientific classification
Domain: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Bacillus
Species: B. anthracis
Binomial name
Bacillus anthracis
Cohn 1872
This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Anthrax.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The causative agent of anthrax is B. anthracis, a nonmotile, Gram-positive, aerobic or facultatively anaerobic, endospore-forming, rod-shaped bacterium. The spores of B. anthracis, which can remain dormant in the environment for decades, are the infectious form, but this vegetative B. anthracis rarely causes disease.[1] The Bacillus may enter the body through the skin, lungs, gastrointestinal system or by injection, after which they will travel to the lymph nodes. The virulence factors will facilitate the translocation of the toxins to the cytosol. The natural reservoirs of Bacillus anthracis include humans, mammals, herbivores, reptiles, and birds.

Historical background

French physician Casimir Davaine (1812-1882) demonstrated the symptoms of anthrax were invariably accompanied by the microbe B. anthracis.[2] German physician Aloys Pollender (1799–1879) is also credited for this discovery. B. anthracis was the first bacterium conclusively demonstrated to cause disease, by Robert Koch in 1876.[3] The species name anthracis is from the Greek anthrax (ἄνθραξ), meaning "coal" and referring to the most common form of the disease, cutaneous anthrax, in which large, black skin lesions are formed.

Biology

B. anthracis, the causative agent of anthrax, is a nonmotile, Gram-positive, aerobic or facultatively anaerobic, endospore-forming, rod-shaped bacterium approximately 4 μm by 1 μm, although under the microscope it frequently appears in chains of cells. Like other Bacillus, Bacillus anthracis is saprophyte, being able to live in vegetation, air, water and soil.[4]

These bacterial cells may occur isolated, form groups of 2 or more cells in the body, or long chains in cultures.[4] In blood smears, smears of tissues or lesion fluid from diagnostic specimens, these chains are two to a few cells in length. In smears made from in vitro cultures, they can appear as endless strings of cells - responsible for the characteristic tackiness of the colonies and for the flocculating nature of broth cultures. Cell cultures appear with a large, grey and curled structure, resembling a "medusa head".[4]

B. anthracis have a characteristic square-ended appearance, traditionally associated with its vegetative state, although this may not always be very clear. In the presence of oxygen, ideally at 32 - 35 ºC, and towards the end of the exponential phase of growth, one ellipsoidal spore (approximately 2 μm by 1 μm in size) is formed within each cell.[5][4] Commonly the spores will be produced once the cell senses scarcity of nutrients.[6]

The spores of B. anthracis, which can remain dormant in the environment for decades, being resistant to heat and disinfectants, are the infectious form, but vegetative B. anthracis rarely causes disease.[7][4]

In the absence of oxygen and under a high partial pressure of Co2, in the presence of bicarbonate, the vegetative cell secretes its polypeptide capsule. This is one of the two established in vivo virulence factors of B. anthracis. The capsule is also a primary diagnostic aid.[5] Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET) and PA and lethal factor (LF) combine to form lethal toxin (LT), the active toxins.[8][9]


Photomicrograph depicting a number of Gram-positive, endospore-forming Bacillus anthracis bacteriaCourtesy: Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)[10]
Scanning electron micrograph (SEM) depicted spores from the Sterne strain of Bacillus anthracis bacteriaCourtesy: Public Health Image Library (PHIL), Centers for Disease Control and Prevention (CDC)[11]

Genome structure

B. anthracis has a single chromosome which is a circular, 5,227,293-bp DNA molecule.[12] It also has two circular, extrachromosomal, double-stranded DNA plasmids, pXO1 and pXO2. Both the pXO1 and pXO2 plasmids are required for full virulence and represent two distinct plasmid families.[13]

Feature Chromosome pXO1 pXO2
Size (bp) 5,227,293 181,677 94,829
Number of genes 5,508 217 113
Replicon coding (%) 84.3 77.1 76.2
Average gene length (nt) 800 645 639
G+C content (%) 35.4 32.5 33.0
rRNA operons 11 0 0
tRNAs 95 0 0
sRNAs 3 2 0
Phage genes 62 0 0
Transposon genes 18 15 6
Disrupted reading frame 37 5 7
Genes with assigned function 2,762 65 38
Conserved hypothetical genes 1,212 22 19
Genes of unknown function 657 8 5
Hypothetical genes 877 122 51

pXO1 plasmid

The pXO1 plasmid (182 kb) contains the genes that encode for the anthrax toxin components: pag (protective antigen, PA), lef (lethal factor, LF), and cya (edema factor, EF). These factors are contained within a 44.8-kb pathogenicity island (PAI). The lethal toxin is a combination of PA with LF and the edema toxin is a combination of PA with EF. The PAI also contains genes which encode a transcriptional activator AtxA and the repressor PagR, both of which regulate the expression of the anthrax toxin genes.[13]

pXO2 plasmid

pXO2 encodes a five-gene operon (capBCADE) which synthesizes a poly-γ-D-glutamic acid (polyglutamate) capsule. This capsule allows B. anthracis to evade the host immune system by protecting itself from phagocytosis. Expression of the capsule operon is activated by the transcriptional regulators AcpA and AcpB, located in the pXO2 pathogenicity island (35 kb). Interestingly, AcpA and AcpB expression are under the control of AtxA from pXO1.[13]

Strains

The 89 known strains of B. anthracis include:

  • Sterne strain (34F2; aka the "Weybridge strain"), used by Max Sterne in his 1930s vaccines
  • Vollum strain, formerly weaponized by the US, UK, and Iraq; isolated from cow in Oxfordshire, UK, in 1935
    • Vollum M-36, virulent British research strain; passed through macaques 36 times
    • Vollum 1B, weaponized by the US and UK in the 1940s-60s
    • Vollum-14578, UK biotesting contaminated Gruinard Island, Scotland, in 1940s
    • V770-NP1-R, the avirulent, nonencapsulated strain used in the BioThrax vaccine
  • Anthrax 836, highly virulent strain weaponized by the USSR; discovered in Kirov in 1953
  • Ames strain, isolated from a cow in Texas in 1981; famously used in AMERITHRAX letter attacks (2001)
    • Ames Ancestor
    • Ames Florida
  • H9401, isolated from human patient in Korea; used in investigational anthrax vaccines[14]

Evolution

Whole genome sequencing has made reconstruction of the B. anthracis phylogeny extremely accurate. A contributing factor to the reconstruction is B. anthracis being monomorphic, meaning it has low genetic diversity, including the absence of any measurable lateral DNA transfer since its derivation as a species. The lack of diversity is due to a short evolutionary history that has precluded mutational saturation in single nucleotide polymorphisms.[15]

A short evolutionary time does not necessarily mean a short chronological time. When DNA is replicated, mistakes occur which become genetic mutations. The buildup of these mutations over time leads to the evolution of a species. During the B. anthracis lifecycle, it spends a significant amount of time in the soil spore reservoir stage, a stage in which DNA replication does not occur. These prolonged periods of dormancy have greatly reduced the evolutionary rate of the organism.[15]

Nearest neighbors

B. anthracis belongs to the B. cereus group consisting of the strains: B. cereus, B. anthracis, B. thuringiensis, B. weihenstephanensis, B. mycoides, and B. pseudomycoides. The first three strains are pathogenic or opportunistic to insects or mammals, while the last three are not considered pathogenic. The strains of this group are genetically and phenotypically heterogeneous overall, but some of the strains are more closely related and phylogenetically intermixed at the chromosome level. The B. cereus group generally exhibits complex genomes and most carry varying numbers of plasmids.[13]

B. cereus is a soil-dwelling bacterium which can colonize the gut of invertebrates as a symbiont[16] and is a frequent cause of food poisoning[17] It produces an emetic toxin, enterotoxins, and other virulence factors.[18] The enterotoxins and virulence factors are encoded on the chromosome, while the emetic toxin is encoded on a 270-kb plasmid, pCER270.[13]

B. thuringiensis is an insect pathogen and is characterized by production of parasporal crystals of insecticidal toxins Cry and Cyt.[19] The genes encoding these proteins are commonly located on plasmids which can be lost from the organism, making it indistinguishable from B. cereus.[13]

Pseudogene

PlcR is a global transcriptional regulator which controls most of the secreted virulence factors in B. cereus and B. thuringiensis. It is chromosomally encoded and is ubiquitous throughout the cell.[20] In B. anthracis, however, the plcR gene contains a single base change at position 640, a nonsense mutation, which creates a dysfunctional protein. While 1% of the B. cereus group carries an inactivated plcR gene, none of them carries the specific mutation found only in B. anthracis.[21]

The plcR gene is part of a two-gene operon with papR.[22][23] The papR gene encodes a small protein which is secreted from the cell and the reimported as a processed heptapeptide forming a quorum-sensing system.[23][24] The lack of PlcR in B. anthracis is a principle characteristic differentiating it from other members of the B. cereus group. While B. cereus and B. thuringiensis depend on the plcR gene for expression of their virulence factors, B. anthracis relies on the pXO1 and pXO2 plasmids for its virulence.[13]

Laboratory research

Components of tea, such as polyphenols, have the ability to inhibit the activity both of B. anthracis and its toxin considerably; spores, however, are not affected. The addition of milk to the tea completely inhibits its antibacterial activity against anthrax.[25] Activity against the B. athracis in the laboratory does not prove that drinking tea affects the course of an infection, since it is unknown how these polyphenols are absorbed and distributed within the body.

Recent research

Advances in genotyping methods have led to improved genetic analysis for variation and relatedness. These methods include multiple-locus variable-number tandem repeat analysis (MLVA) and typing systems using canonical single-nucleotide polymorphisms. The Ames ancestor chromosome was sequenced in 2003[12] and contributes to the identification of genes involved in the virulence of B. anthracis. Recently, B. anthracis isolate H9401 was isolated from a Korean patient suffering from gastrointestinal anthrax. The goal of the Republic of Korea is to use this strain as a challenge strain to develop a recombinant vaccine against anthrax.[14]

The H9401 strain isolated in the Republic of Korea was sequenced using 454 GS-FLX technology and analyzed using several bioinformatics tools to align, annotate, and compare H9401 to other B. anthracis strains. The sequencing coverage level suggests a molecular ratio of pXO1:pXO2:chromosome as 3:2:1 which is identical to the Ames Florida and Ames Ancestor strains. H9401 has 99.679% sequence homology with Ames Ancestor with an amino acid sequence homology of 99.870%. H9401 has a circular chromosome (5,218,947 bp with 5,480 predicted ORFs), the pXO1 plasmid (181,700 bp with 202 predicted ORFs), and the pXO2 plasmid (94,824 bp with 110 predicted ORFs).[14] As compared to the Ames Ancestor chromosome above, the H9401 chromosome is about 8.5 kb smaller. Due to the high pathogenecity and sequence similarity to the Ames Ancestor, H9401 will be used as a reference for testing the efficacy of candidate anthrax vaccines by the Repbulic of Korea.[14]

Host interactions

As with most other pathogenic bacteria, B. anthracis must acquire iron to grow and proliferate in its host environment. The most readily available iron sources for pathogenic bacteria are the heme groups used by the host in the transport of oxygen. To scavenge heme from host hemoglobin and myoglobin, B. anthracis uses two secretory siderophore proteins, IsdX1 and IsdX2. These proteins can separate heme from hemoglobin, allowing surface proteins of B. anthracis to transport it into the cell.[26]

Origin

Bacillus anthracis is thought to have originated in Egypt and Mesopotamia. Many scholars think that in Moses’ time, during the 10 plagues of Egypt, anthrax may have caused what was known as the fifth plague, described as a sickness affecting horses, cattle, sheep, camels and oxen.

Tropism

After entering the body (through the skin, lungs, gastrointestinal tract or by injection), B. anthracis spores are believed to germinate locally or be transported by phagocytic cells to the lymphatics and regional lymph nodes, where they germinate.[9][27] After binding to cell surface receptors, the PA portion of the complexes facilitates translocation of the toxins to the cytosol.[28][9]

Natural Reservoir

Natural reservoirs of Bacillus anthracis include:[5][4][9]

  • Humans
  • Mammals
  • Herbivores
  • Reptiles
  • Birds


References

  1. ↑ Sean V. Shadomy & Theresa L. Smith (2008). "Zoonosis update. Anthrax". Journal of the American Veterinary Medical Association. 233 (1): 63–72. doi:10.2460/javma.233.1.63. PMID 18593313. Unknown parameter |month= ignored (help)
  2. ↑ Théodoridès, J (April 1966). "Casimir Davaine (1812-1882): a precursor of Pasteur". Medical history. 10 (2): 155–65. doi:10.1017/S0025727300010942. PMC 1033586. PMID 5325873.
  3. ↑ Koch, R. (1876) "Untersuchungen über Bakterien: V. Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des Bacillus anthracis" (Investigations into bacteria: V. The etiology of anthrax, based on the ontogenesis of Bacillus anthracis), Cohns Beitrage zur Biologie der Pflanzen, vol. 2, no. 2, pages 277–310.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Bhatnagar, Rakesh; Batra, Smriti (2001). "Anthrax Toxin". Critical Reviews in Microbiology. 27 (3): 167–200. doi:10.1080/20014091096738. ISSN 1040-841X.
  5. ↑ 5.0 5.1 5.2 "Anthrax in Humans and Animals" (PDF).
  6. ↑ Spencer RC (2003). "Bacillus anthracis". J Clin Pathol. 56 (3): 182–7. PMC 1769905. PMID 12610093.
  7. ↑ Sean V. Shadomy & Theresa L. Smith (2008). "Zoonosis update. Anthrax". Journal of the American Veterinary Medical Association. 233 (1): 63–72. doi:10.2460/javma.233.1.63. PMID 18593313. Unknown parameter |month= ignored (help)
  8. ↑ Mahtab Moayeri & Stephen H. Leppla (2004). "The roles of anthrax toxin in pathogenesis". Current opinion in microbiology. 7 (1): 19–24. doi:10.1016/j.mib.2003.12.001. PMID 15036135. Unknown parameter |month= ignored (help)
  9. ↑ 9.0 9.1 9.2 9.3 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
  10. ↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  11. ↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  12. ↑ 12.0 12.1 Read, TD (May 1, 2003). "The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria". Nature. 423 (6935): 81–6. doi:10.1038/nature01586. PMID 12721629. Unknown parameter |coauthors= ignored (help)
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 Kolstø, Anne-Brit; Tourasse, Nicolas J.; Økstad, Ole Andreas (1 October 2009). "What Sets Apart from Other Species?". Annual Review of Microbiology. 63 (1): 451–476. doi:10.1146/annurev.micro.091208.073255.
  14. ↑ 14.0 14.1 14.2 14.3 Chun, J.-H.; Hong, K.-J.; Cha, S. H.; Cho, M.-H.; Lee, K. J.; Jeong, D. H.; Yoo, C.-K.; Rhie, G.-e. (18 July 2012). "Complete Genome Sequence of Bacillus anthracis H9401, an Isolate from a Korean Patient with Anthrax". Journal of Bacteriology. 194 (15): 4116–4117. doi:10.1128/JB.00159-12. PMC 3416559. PMID 22815438.
  15. ↑ 15.0 15.1 Keim, Paul; Gruendike, Jeffrey M.; Klevytska, Alexandra M.; Schupp, James M.; Challacombe, Jean; Okinaka, Richard (1 December 2009). "The genome and variation of Bacillus anthracis". Molecular Aspects of Medicine. 30 (6): 397–405. doi:10.1016/j.mam.2009.08.005. PMC 3034159. PMID 19729033.
  16. ↑ Jensen, G. B.; Hansen, B. M.; Eilenberg, J.; Mahillon, J. (18 July 2003). "The hidden lifestyles of Bacillus cereus and relatives". Environmental Microbiology. 5 (8): 631–640. doi:10.1046/j.1462-2920.2003.00461.x. PMID 12871230.
  17. ↑ Drobniewski, FA (October 1993). "Bacillus cereus and related species". Clinical Microbiology Reviews. 6 (4): 324–38. PMC 358292. PMID 8269390.
  18. ↑ Stenfors Arnesen, Lotte P.; Fagerlund, Annette; Granum, Per Einar (1 July 2008). "From soil to gut: and its food poisoning toxins". FEMS Microbiology Reviews. 32 (4): 579–606. doi:10.1111/j.1574-6976.2008.00112.x. PMID 18422617.
  19. ↑ Schnepf, E; Crickmore, N; Van Rie, J; Lereclus, D; Baum, J; Feitelson, J; Zeigler, DR; Dean, DH (September 1998). "Bacillus thuringiensis and its pesticidal crystal proteins". Microbiology and molecular biology reviews : MMBR. 62 (3): 775–806. PMC 98934. PMID 9729609.
  20. ↑ Agaisse, H; Gominet, M; Okstad, OA; Kolstø, AB; Lereclus, D (June 1999). "PlcR is a pleiotropic regulator of extracellular virulence factor gene expression in Bacillus thuringiensis". Molecular microbiology. 32 (5): 1043–53. doi:10.1046/j.1365-2958.1999.01419.x. PMID 10361306.
  21. ↑ Slamti, L; Perchat, S; Gominet, M; Vilas-Bôas, G; Fouet, A; Mock, M; Sanchis, V; Chaufaux, J; Gohar, M; Lereclus, D (June 2004). "Distinct mutations in PlcR explain why some strains of the Bacillus cereus group are nonhemolytic". Journal of bacteriology. 186 (11): 3531–8. doi:10.1128/JB.186.11.3531-3538.2004. PMC 415780. PMID 15150241.
  22. ↑ Okstad, OA; Gominet, M; Purnelle, B; Rose, M; Lereclus, D; Kolstø, AB (November 1999). "Sequence analysis of three Bacillus cereus loci carrying PIcR-regulated genes encoding degradative enzymes and enterotoxin". Microbiology (Reading, England). 145 (11): 3129–38. PMID 10589720.
  23. ↑ 23.0 23.1 Slamti, L; Lereclus, D (Sep 2, 2002). "A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group". The EMBO Journal. 21 (17): 4550–9. doi:10.1093/emboj/cdf450. PMC 126190. PMID 12198157.
  24. ↑ Bouillaut, L; Perchat, S; Arold, S; Zorrilla, S; Slamti, L; Henry, C; Gohar, M; Declerck, N; Lereclus, D (June 2008). "Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides". Nucleic Acids Research. 36 (11): 3791–801. doi:10.1093/nar/gkn149. PMC 2441798. PMID 18492723.
  25. ↑ "Anthrax and tea". Society for Applied Microbiology. 2011-12-21. Retrieved 2011-12-21.
  26. ↑ Maresso AW, Garufi G, Schneewind O (2008). "Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from Hemoglobin". PLOS Pathogens. 4(8): e1000132.
  27. ↑ Ross, Joan M. (1957). "The pathogenesis of anthrax following the administration of spores by the respiratory route". The Journal of Pathology and Bacteriology. 73 (2): 485–494. doi:10.1002/path.1700730219. ISSN 0368-3494.
  28. ↑ Moayeri, M (2004). "The roles of anthrax toxin in pathogenesis". Current Opinion in Microbiology. 7 (1): 19–24. doi:10.1016/j.mib.2003.12.001. ISSN 1369-5274.

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