Editing Streptococcus pyogenes (section)

=== Virulence factors ===

''S. pyogenes'' has several [[virulence factor]]s that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.<ref name="Baron">{{cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.824|title=Streptococcus. ''In:'' Baron's Medical Microbiology|author=Patterson MJ|publisher=University of Texas Medical Branch|year=1996|isbn=978-0-9631172-1-2|editor=Baron S|edition=4th|display-editors=etal|chapter=Streptococcus}}</ref>  A carbohydrate-based [[bacterial capsule]] composed of [[hyaluronic acid]] surrounds the bacterium, protecting it from [[phagocytosis]] by [[neutrophils]].<ref name="Sherris" /> In addition, the capsule and several factors embedded in the cell wall, including [[M protein (Streptococcus)|M protein]], [[lipoteichoic acid]], and protein F (SfbI) facilitate attachment to various host cells.<ref name="Bisno_2003">{{cite journal | vauthors = Bisno AL, Brito MO, Collins CM | title = Molecular basis of group A streptococcal virulence | journal = The Lancet. Infectious Diseases | volume = 3 | issue = 4 | pages = 191–200 | date = April 2003 | pmid = 12679262 | doi = 10.1016/S1473-3099(03)00576-0 }}</ref>  M protein also inhibits [[opsonization]] by the alternative [[complement system|complement pathway]] by binding to host complement regulators.  The M protein found on some serotypes is also able to prevent opsonization by binding to [[fibrinogen]].<ref name="Sherris" />  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.<ref>{{cite journal | vauthors = Engel ME, Muhamed B, Whitelaw AC, Musvosvi M, Mayosi BM, Dale JB | title = Group A streptococcal emm type prevalence among symptomatic children in Cape Town and potential vaccine coverage | journal = The Pediatric Infectious Disease Journal | volume = 33 | issue = 2 | pages = 208–210 | date = February 2014 | pmid = 23934204 | pmc = 3947201 | doi = 10.1097/INF.0b013e3182a5c32a }}</ref>

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!Name
!Description
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|Streptolysin O
|An [[exotoxin]], one of the bases of the organism's beta-hemolytic property, streptolysin O causes an immune response and detection of antibodies to it; antistreptolysin O (ASO) can be clinically used to confirm a recent infection.  It is damaged by oxygen.
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|Streptolysin S
|A cardiotoxic exotoxin, another beta-hemolytic component, not immunogenic and O<sub>2</sub> stable: A potent cell poison affecting many types of cell including neutrophils, platelets, and subcellular organelles.
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|Streptococcal pyrogenic exotoxin A (SpeA)
|rowspan=2|[[Superantigen]]s secreted by many strains of ''S. pyogenes'':  This [[streptococcal pyrogenic exotoxin]] is responsible for the rash of scarlet fever and many of the symptoms of streptococcal toxic shock syndrome, also known as toxic shock like syndrome (TSLS).
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|Streptococcal pyrogenic exotoxin C (SpeC)
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|Streptococcal pyrogenic exotoxin B (SpeB)
|A cysteine protease and the predominant secreted protein. Multiple actions, including degrading the extracellular matrix, cytokines, complement components, and immunoglobulins. Also called [[streptopain]].<ref>{{cite journal | vauthors = Nelson DC, Garbe J, Collin M | title = Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins | journal = Biological Chemistry | volume = 392 | issue = 12 | pages = 1077–1088 | date = December 2011 | pmid = 22050223 | doi = 10.1515/BC.2011.208 | s2cid = 207441558 | doi-access = free }}</ref>
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|[[Streptokinase]]
|Enzymatically activates [[plasminogen]], a proteolytic enzyme, into [[plasmin]], which in turn digests [[fibrin]] and other proteins
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|[[Hyaluronidase]]
|Hyaluronidase is widely assumed to facilitate 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 encodes the enzyme.  Moreover, the few isolates 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 | vauthors = Starr CR, Engleberg NC | title = Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus | journal = Infection and Immunity | volume = 74 | issue = 1 | pages = 40–48 | date = January 2006 | pmid = 16368955 | pmc = 1346594 | doi = 10.1128/IAI.74.1.40-48.2006 }}</ref>  Thus, the true role of hyaluronidase in pathogenesis, if any, remains unknown.
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|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 NETs' web of DNA, to which are bound [[neutrophil]] [[serine protease]]s that can kill the bacteria.<ref name=Buchanan_2006>{{cite journal | vauthors = Buchanan JT, Simpson AJ, Aziz RK, Liu GY, Kristian SA, Kotb M, Feramisco J, Nizet V | display-authors = 6 | title = DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps | journal = Current Biology | volume = 16 | issue = 4 | pages = 396–400 | date = February 2006 | pmid = 16488874 | doi = 10.1016/j.cub.2005.12.039 | bibcode = 2006CBio...16..396B | s2cid = 667804 }}</ref>
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|[[Complement component 5a|C5a]] [[peptidase]]
|C5a peptidase cleaves a potent [[neutrophil]] chemotaxin called [[Complement component 5a|C5a]], which is produced by the [[complement system]].<ref name=Wexler_1985>{{cite journal | vauthors = Wexler DE, Chenoweth DE, Cleary PP | title = Mechanism of action of the group A streptococcal C5a inactivator | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 82 | issue = 23 | pages = 8144–8148 | date = December 1985 | pmid = 3906656 | pmc = 391459 | doi = 10.1073/pnas.82.23.8144 | doi-access = free | bibcode = 1985PNAS...82.8144W }}</ref>  C5a peptidase is necessary to minimize the influx of [[neutrophil]]s early in infection as the bacteria are attempting to colonize the host's tissue.<ref name="Ji 1996">{{cite journal | vauthors = Ji Y, McLandsborough L, Kondagunta A, Cleary PP | title = C5a peptidase alters clearance and trafficking of group A streptococci by infected mice | journal = Infection and Immunity | volume = 64 | issue = 2 | pages = 503–510 | date = February 1996 | pmid = 8550199 | pmc = 173793 | doi = 10.1128/IAI.64.2.503-510.1996 }}</ref> 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="Hidalgo-Grass 2006">{{cite journal | vauthors = Hidalgo-Grass C, Mishalian I, Dan-Goor M, Belotserkovsky I, Eran Y, Nizet V, Peled A, Hanski E | display-authors = 6 | title = A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues | journal = The EMBO Journal | volume = 25 | issue = 19 | pages = 4628–4637 | date = October 2006 | pmid = 16977314 | pmc = 1589981 | doi = 10.1038/sj.emboj.7601327 }}</ref>
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|Streptococcal chemokine protease
|The affected tissue of patients with severe cases of [[necrotizing fasciitis]] are devoid of neutrophils.<ref name=Hidalgo-Grass_2004>{{cite journal | vauthors = Hidalgo-Grass C, Dan-Goor M, Maly A, Eran Y, Kwinn LA, Nizet V, Ravins M, Jaffe J, Peyser A, Moses AE, Hanski E | display-authors = 6 | 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 | date = February 2004 | pmid = 15001327 | doi = 10.1016/S0140-6736(04)15643-2 | s2cid = 7219898 }}</ref> The [[serine protease]] ScpC, which is released by ''S. pyogenes'', is responsible for preventing the migration of neutrophils to the spreading infection. ScpC degrades the [[chemokine]] [[Interleukin 8|IL-8]], which would otherwise attract [[neutrophil]]s to the site of infection.<ref name="Ji 1996"/><ref name="Hidalgo-Grass 2006"/>
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