Sandbox: GAS pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 6: Line 6:
===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>
{| class="wikitable"
!Virulence factors
! colspan="2" |Mechanism of action
|-
|Streptolysin O and S
|
|
|-
|Streptococcal pyrogenic exotoxins A and C
|
|
|-
|Streptokinase
|
|
|-
|Hyalourinidase
|
|
|-
|Streptodornase
|
|
|-
|[[C5a]] [[peptidase]]
|
|
|-
|Streptococcal chemokine protease
|
|
|}
   
   
''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'' 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.

Revision as of 14:22, 24 May 2017

Transmission

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

  • Direct inter-personal 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
Streptolysin O and S
Streptococcal pyrogenic exotoxins A and C
Streptokinase
Hyalourinidase
Streptodornase
C5a peptidase
Streptococcal chemokine protease

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.[2] 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.[3] M protein also inhibits opsonization by the alternative 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 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 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.[4] Thus, the true role of hyaluronidase in pathogenesis, if any, remains unknown.
Streptodornase
Most strains of S. pyogenes secrete up to four different DNases, 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 proteases that can kill the bacteria.[5]
C5a peptidase
C5a peptidase cleaves a potent neutrophil chemotaxin called C5a, which is produced by the complement system.[6] C5a peptidase is necessary to minimize the influx of neutrophils early in infection as the bacteria are attempting to colonize the host's tissue.[7].
Streptococcal chemokine protease
The affected tissue of patients with severe cases of necrotizing fasciitis are devoid of neutrophils.[8]. The serine protease ScpC, which is released by S. pyogenes, is responsible for preventing the migration of neutrophils to the spreading infection.[9] 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.[7][9]

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, 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

  • The initial step in pathogenesis of group a streptococcus, in order to cause infection, is the adhesion and colonization of the bacteria to the epithelial cells.[10][11].The bacteria adheses and invades the cell leading to tissue destruction and infection.

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. ↑ Patterson MJ (1996). Streptococcus. In: Baron's Medical Microbiology (Baron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
  3. ↑ Bisno AL, Brito MO, Collins CM (2003). "Molecular basis of group A streptococcal virulence". Lancet Infect Dis. 3 (4): 191–200. PMID 12679262.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 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.
  9. ↑ 9.0 9.1 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.
  10. ↑ Courtney HS, Hasty DL, Dale JB (2002). "Molecular mechanisms of adhesion, colonization, and invasion of group A streptococci". Ann Med. 34 (2): 77–87. PMID 12108578.
  11. ↑ Moschioni M, Pansegrau W, Barocchi MA (2010). "Adhesion determinants of the Streptococcus species". Microb Biotechnol. 3 (4): 370–88. doi:10.1111/j.1751-7915.2009.00138.x. PMC 3815805. PMID 21255337.
Retrieved from "https://www.wikidoc.org/index.php?title=Sandbox:_GAS_pathophysiology&oldid=1313152"