Sandbox: GAS pathophysiology: Difference between revisions

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===Transmission===
Group A streptococcal infection can be transmitted by the following:<ref name="pmid27312939">{{cite journal| author=Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ| title=Streptococcus pyogenes adhesion and colonization. | journal=FEBS Lett | year= 2016 | volume= 590 | issue= 21 | pages= 3739-3757 | pmid=27312939 | doi=10.1002/1873-3468.12254 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27312939  }} </ref>
*Direct inoculation transmission
*Infected airborne droplets
===Virulence factors===  
===Virulence factors===  
Group A streptococcus are responsible for various diseases ranging from mild to life threatening cases. The bacteria depends mainly on many virulence factors which are responsible for the pathogenesis of the infections.<ref name="pmid27312939">{{cite journal| author=Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ| title=Streptococcus pyogenes adhesion and colonization. | journal=FEBS Lett | year= 2016 | volume= 590 | issue= 21 | pages= 3739-3757 | pmid=27312939 | doi=10.1002/1873-3468.12254 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27312939  }} </ref>
Group A streptococcus are responsible for various diseases ranging from mild to life threatening cases. The bacteria depends mainly on many virulence factors which are responsible for the pathogenesis of the infections.<ref name="pmid27312939">{{cite journal| author=Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ| title=Streptococcus pyogenes adhesion and colonization. | journal=FEBS Lett | year= 2016 | volume= 590 | issue= 21 | pages= 3739-3757 | pmid=27312939 | doi=10.1002/1873-3468.12254 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27312939  }} </ref>
''S. pyogenes'' has several [[virulence]] factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.<ref name=Baron>{{cite book | author = Patterson  MJ | title = Streptococcus. ''In:'' Baron's Medical Microbiology ''(Baron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | id = [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.824 (via NCBI Bookshelf)] ISBN 0-9631172-1-1 }}</ref>  A [[carbohydrate]] capsule composed of [[hyaluronic acid]] surrounds the bacterium, protecting it from [[phagocytosis]] by [[neutrophils]]. In addition, the capsule and several factors embedded in the cell wall, including M protein, [[lipoteichoic acid]], and protein F (SfbI) facilitate attachment to various host cells.<ref name=Bisno_2003>{{cite journal | author=Bisno AL, Brito MO, Collins CM | title=Molecular basis of group A streptococcal virulence | journal=Lancet Infect Dis | year=2003 | pages=191-200 | volume=3 | issue=4 | id={{PMID|12679262}} }}</ref>  M protein also inhibits [[opsonization]] by the alternative [[complement system|complement pathway]] by binding to host complement regulators.  M protein found on some serotypes are also able to prevent opsonization by binding to [[fibrinogen]].  However, the M protein is also the weakest point in this pathogen's defense as [[Antibody|antibodies]] produced by the [[immune system]] against M protein target the bacteria for engulfment by [[phagocytes]].  M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.
''S. pyogenes'' releases a number of proteins, including several virulence factors, into its host:
;Streptolysin O and S
:These are [[Exotoxin|toxins]] which are the basis of the organism's beta-hemolytic property.  Streptolysin O is a potent cell poison affecting many types of cell including neutrophils, platelets, and sub-cellular organelles. It causes an immune response and detection of antibodies to it; antistreptolysin O (ASO) can be clinically used to confirm a recent infection. 
;Streptococcal pyrogenic [[exotoxins]] (Spe) A and C
:SpeA and SpeC are superantigens secreted by many strains of ''S. pyogenes''.  These pyrogenic exotoxins are responsible for the [[rash]] of [[scarlet fever]] and many of the symptoms of streptococcal [[toxic shock syndrome]].
;[[Streptokinase]]
:Enzymatically activates [[plasminogen]], a proteolytic enzyme, into [[plasmin]] which in turn digests [[fibrin]] and other proteins. 
;[[Hyaluronidase]]
:It is widely assumed that [[hyaluronidase]] facillitates the spread of the bacteria through tissues by breaking down [[hyaluronic acid]], an important component of [[connective tissue]].  However, very few isolates of ''S. pyogenes'' are capable of secreting active hyaluronidase due to mutations in the gene that encode the enzyme.  Moreover, the few isolates that are capable of secreting hyaluronidase do not appear to need it to spread through tissues or to cause skin lesions.<ref name=Starr_2006>{{cite journal |author=Starr C, Engleberg N |title=Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus |journal=Infect Immun |volume=74 |issue=1 |pages=40-8 |year=2006 |id=PMID 16368955}}</ref>  Thus, the true role of hyaluronidase in pathogenesis, if any, remains unknown.
;Streptodornase
:Most strains of ''S. pyogenes'' secrete up to four different [[DNase]]s, which are sometimes called ''streptodornase''. The DNases protect the bacteria from being trapped in [[neutrophil extracellular traps]] (NETs) by digesting the NET's web of DNA, to which are bound [[neutrophil]] [[serine protease]]s that can kill the bacteria.<ref name=Buchanan_2006>{{cite journal |author=Buchanan J, Simpson A, Aziz R, Liu G, Kristian S, Kotb M, Feramisco J, Nizet V |title=DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps |journal=Curr Biol |volume=16 |issue=4 |pages=396-400 |year=2006 |id=PMID 16488874}}</ref>
;[[C5a]] [[peptidase]]
:C5a peptidase cleaves a potent [[neutrophil]] chemotaxin called [[C5a]], which is produced by the complement system.<ref name=Wexler_1985>{{cite journal |author=Wexler D, Chenoweth D, Cleary P |title=Mechanism of action of the group A streptococcal C5a inactivator |journal=Proc Natl Acad Sci U S A |volume=82 |issue=23 |pages=8144-8 |year=1985 |id=PMID 3906656}}</ref>  C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.<ref name="Ji 1996">{{cite journal |author=Ji Y, McLandsborough L, Kondagunta A, Cleary P |title=C5a peptidase alters clearance and trafficking of group A streptococci by infected mice |journal=Infect Immun |volume=64 |issue=2 |pages=503-10 |year=1996 |id=PMID 8550199}}</ref>. 
;Streptococcal chemokine protease
:The affected tissue of patients with severe cases of [[necrotizing fasciitis]] are devoid of [[neutrophil]]s.<ref name=Hidalgo-Grass_2004>{{cite journal |author=Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn L, Nizet V, Ravins M, Jaffe J, Peyser A, Moses A, Hanski E |title=Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections |journal=Lancet |volume=363 |issue=9410 |pages=696-703 |year=2004 |id=PMID 15001327}}</ref>.  The [[serine protease]] ScpC, which is released by ''S. pyogenes'', is responsible for preventing the migration of neutrophils to the spreading infection.<ref name="Hidalgo-Grass 2006">{{cite journal |author=Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E |title=A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues |journal=EMBO J |volume=25 |issue=19 |pages=4628-37 |year=2006 |id=PMID 16977314}}</ref>  ScpC degrades the [[chemokine]] [[IL-8]], which would otherwise attract [[neutrophil]]s to the site of infection.  C5a peptidase, although required to degrade the neutrophil chemotaxin C5a in the early stages of infection, is not required for ''S. pyogenes'' to prevent the influx of neutrophils as the bacteria spread through the [[fascia]].<ref name="Ji 1996"/><ref name="Hidalgo-Grass 2006"/>
====Severe streptococcal infections====
Some strains of group A streptococci (GAS) cause severe infection. Those at greatest risk include children with [[chickenpox]]; persons with [[suppressed immune systems]]; [[burn]] victims; elderly persons with [[cellulitis]], [[diabetes]], blood vessel disease, or [[cancer]]; and persons taking [[steroid]] treatments or [[chemotherapy]]. [[Intravenous drug]] users also are at high risk. GAS is an important cause of [[puerperal fever]] world-wide, causing serious infection and, if not promptly diagnosed and treated, death in newly delivered mothers. Severe GAS disease may also occur in healthy persons with no known risk factors.
All severe GAS infections may lead to [[Shock (medical)|shock]], [[multisystem organ failure]], and [[death]]. Early recognition and treatment are critical. Diagnostic tests include [[blood counts]] and [[urinalysis]] as well as cultures of blood or fluid from a wound site. The antibiotic of choice is [[penicillin]], to which GAS is particularly susceptible and has never been found to be resistant.  [[Erythromycin]] and [[clindamycin]] are other treatment options, though resistance to these antibiotics exists.


===Pathogenesis===
{| class="wikitable"
!Virulence factors
!Mechanism of action
|-
|M - protein
|
* The most important virulence factor.
* It prevents the phagocytosis of the bacteria by binding to the fibrinogen and prevents binding the complement to the bacterial cell wall.   
|-
|Streptolysin O and S
|
* Streptolysin O works on killing the differecnt cells like the neutrophils, platelets and the sub-cellular organelles.
|-
|Streptococcal pyrogenic exotoxins A and C
|
* SpeA and SpeC are superantigens secreted by many strains of ''S. pyogenes''.  These pyrogenic exotoxins are responsible for the [[rash]] of [[scarlet fever]] and many of the symptoms of streptococcal [[toxic shock syndrome]].
|-
|Streptokinase
|
* Enzymatically activates [[plasminogen]] which is a proteolytic enzyme into [[plasmin]] which in turn digests [[fibrin]] and other proteins.
|-
|Hyalourinidase
|
* It helps the bacteria to spread through the tissue by destroying the hyaluronic acid which is a connective tissue component.<ref name=Starr_2006>{{cite journal |author=Starr C, Engleberg N |title=Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus |journal=Infect Immun |volume=74 |issue=1 |pages=40-8 |year=2006 |id=PMID 16368955}}</ref>
|-
|Streptodornase
|
* Most strains of ''S. pyogenes'' secrete up to four different [[DNase]]s, which are sometimes called ''streptodornase''. The DNases protect the bacteria from being trapped in [[neutrophil extracellular traps]] (NETs) by digesting the NET's web of DNA, to which are bound [[neutrophil]] [[serine protease]]s that can kill the bacteria.<ref name=Buchanan_2006>{{cite journal |author=Buchanan J, Simpson A, Aziz R, Liu G, Kristian S, Kotb M, Feramisco J, Nizet V |title=DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps |journal=Curr Biol |volume=16 |issue=4 |pages=396-400 |year=2006 |id=PMID 16488874}}</ref>
|-
|[[C5a]] [[peptidase]]
|
*C5a peptidase cleaves a potent [[neutrophil]] chemotaxin called [[C5a]], which is produced by the complement system.<ref name=Wexler_1985>{{cite journal |author=Wexler D, Chenoweth D, Cleary P |title=Mechanism of action of the group A streptococcal C5a inactivator |journal=Proc Natl Acad Sci U S A |volume=82 |issue=23 |pages=8144-8 |year=1985 |id=PMID 3906656}}</ref>  C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.<ref name="Ji 1996">{{cite journal |author=Ji Y, McLandsborough L, Kondagunta A, Cleary P |title=C5a peptidase alters clearance and trafficking of group A streptococci by infected mice |journal=Infect Immun |volume=64 |issue=2 |pages=503-10 |year=1996 |id=PMID 8550199}}</ref>.
|-
|Streptococcal chemokine protease
|
*The affected tissue of patients with severe cases of [[necrotizing fasciitis]] are devoid of [[neutrophil]]s.<ref name=Hidalgo-Grass_2004>{{cite journal |author=Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn L, Nizet V, Ravins M, Jaffe J, Peyser A, Moses A, Hanski E |title=Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections |journal=Lancet |volume=363 |issue=9410 |pages=696-703 |year=2004 |id=PMID 15001327}}</ref>.  The [[serine protease]] ScpC, which is released by ''S. pyogenes'', is responsible for preventing the migration of neutrophils to the spreading infection.<ref name="Hidalgo-Grass 2006">{{cite journal |author=Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E |title=A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues |journal=EMBO J |volume=25 |issue=19 |pages=4628-37 |year=2006 |id=PMID 16977314}}</ref>  ScpC degrades the [[chemokine]] [[IL-8]], which would otherwise attract [[neutrophil]]s to the site of infection.  C5a peptidase, although required to degrade the neutrophil chemotaxin C5a in the early stages of infection, is not required for ''S. pyogenes'' to prevent the influx of neutrophils as the bacteria spread through the [[fascia]].<ref name="Ji 1996"/><ref name="Hidalgo-Grass 2006"/>
|}


==References==  
==References==  
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 21:43, 29 May 2017

Transmission

Group A streptococcal infection can be transmitted by the following:[1]

  • Direct inoculation transmission
  • Infected airborne droplets

Virulence factors

Group A streptococcus are responsible for various diseases ranging from mild to life threatening cases. The bacteria depends mainly on many virulence factors which are responsible for the pathogenesis of the infections.[1]

Virulence factors Mechanism of action
M - protein
  • The most important virulence factor.
  • It prevents the phagocytosis of the bacteria by binding to the fibrinogen and prevents binding the complement to the bacterial cell wall.
Streptolysin O and S
  • Streptolysin O works on killing the differecnt cells like the neutrophils, platelets and the sub-cellular organelles.
Streptococcal pyrogenic exotoxins A and C
  • SpeA and SpeC are superantigens secreted by many strains of S. pyogenes. These pyrogenic exotoxins are responsible for the rash of scarlet fever and many of the symptoms of streptococcal toxic shock syndrome.
Streptokinase
  • Enzymatically activates plasminogen which is a proteolytic enzyme into plasmin which in turn digests fibrin and other proteins.
Hyalourinidase
  • It helps the bacteria to spread through the tissue by destroying the hyaluronic acid which is a connective tissue component.[2]
Streptodornase
C5a peptidase
  • C5a peptidase cleaves a potent neutrophil chemotaxin called C5a, which is produced by the complement system.[4] C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.[5].
Streptococcal chemokine protease
  • The affected tissue of patients with severe cases of necrotizing fasciitis are devoid of neutrophils.[6]. The serine protease ScpC, which is released by S. pyogenes, is responsible for preventing the migration of neutrophils to the spreading infection.[7] ScpC degrades the chemokine IL-8, which would otherwise attract neutrophils to the site of infection. C5a peptidase, although required to degrade the neutrophil chemotaxin C5a in the early stages of infection, is not required for S. pyogenes to prevent the influx of neutrophils as the bacteria spread through the fascia.[5][7]

References

  1. ↑ 1.0 1.1 Brouwer S, Barnett TC, Rivera-Hernandez T, Rohde M, Walker MJ (2016). "Streptococcus pyogenes adhesion and colonization". FEBS Lett. 590 (21): 3739–3757. doi:10.1002/1873-3468.12254. PMID 27312939.
  2. ↑ Starr C, Engleberg N (2006). "Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus". Infect Immun. 74 (1): 40–8. PMID 16368955.
  3. ↑ Buchanan J, Simpson A, Aziz R, Liu G, Kristian S, Kotb M, Feramisco J, Nizet V (2006). "DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps". Curr Biol. 16 (4): 396–400. PMID 16488874.
  4. ↑ Wexler D, Chenoweth D, Cleary P (1985). "Mechanism of action of the group A streptococcal C5a inactivator". Proc Natl Acad Sci U S A. 82 (23): 8144–8. PMID 3906656.
  5. ↑ 5.0 5.1 Ji Y, McLandsborough L, Kondagunta A, Cleary P (1996). "C5a peptidase alters clearance and trafficking of group A streptococci by infected mice". Infect Immun. 64 (2): 503–10. PMID 8550199.
  6. ↑ Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn L, Nizet V, Ravins M, Jaffe J, Peyser A, Moses A, Hanski E (2004). "Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections". Lancet. 363 (9410): 696–703. PMID 15001327.
  7. ↑ 7.0 7.1 Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E (2006). "A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues". EMBO J. 25 (19): 4628–37. PMID 16977314.
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