Editing Streptococcus pyogenes

{{Short description|Species of bacterium}}
{{Use mdy dates|date=April 2024}}
{{Speciesbox
| image = Streptococcus Pyogenes (Group A Strep) (52602981880).jpg
| image_caption = False-color scanning electron micrograph of chain of ''Streptococcus pyogenes'' bacteria (yellow)
| genus = Streptococcus
| species = pyogenes
| authority = Rosenbach 1884
| synonyms =
| synonyms_ref =
}}

'''''Streptococcus pyogenes''''' is a [[species]] of [[Gram-positive]], aerotolerant [[bacteria]] in the genus ''[[Streptococcus]]''.  These bacteria are [[extracellular]], and made up of non-motile and non-sporing [[cocci]] (round cells) that tend to link in chains. They are clinically important for humans, as they are an infrequent, but usually [[Pathogenic bacteria|pathogenic]], part of the [[skin microbiota]] that can cause [[group A streptococcal infection]].  ''S. pyogenes''  is the predominant species harboring the [[Lancefield grouping|Lancefield]] group A [[antigen]], and is often called '''group A ''Streptococcus''''' ('''GAS''').  However, both ''[[Streptococcus dysgalactiae]]'' and the ''[[Streptococcus anginosus]]'' group can possess group A antigen as well.  Group A streptococci, when grown on [[blood agar]], typically produce small (2–3&nbsp;mm) zones of [[beta-hemolysis]], a complete [[Lysis|destruction]] of [[red blood cell]]s. The name '''group A (beta-hemolytic) ''Streptococcus''''' is thus also used.<ref name=PSDS>{{cite web|url=http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/strep-pyogenes-eng.php |title=Streptococcus pyogenes - Pathogen Safety Data Sheets |publisher=Government of Canada, Public Health Agency of Canada|date=September 26, 2001 }}</ref>

The species name is derived from Greek words meaning 'a chain' ({{lang|el-Latn|streptos}}) of berries ({{lang|la|coccus}} [Latinized from {{lang|el-Latn|kokkos}}]) and [[pus]] ({{lang|el-Latn|pyo}})-forming (''genes''), since a number of infections caused by the bacterium produce pus.  The main criterion for differentiation between ''[[Staphylococcus]]'' spp. and ''Streptococcus'' spp. is the [[catalase test]].  Staphylococci are catalase positive whereas streptococci are catalase-negative.<ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref>  ''S. pyogenes'' can be [[microbiological culture|cultured]] on fresh blood agar plates. The [[Pyrrolidonyl-β-naphthylamide|PYR]] test allows for the differentiation of ''Streptococcus pyogenes'' from other morphologically similar beta-hemolytic streptococci (including ''S. dysgalactiae'' subsp. ''esquismilis'') as ''S. pyogenes'' will produce a positive test result.<ref>{{cite book| vauthors = Spellerberg B, Brandt C | chapter = Chapter 29: Laboratory Diagnosis of Streptococcus pyogenes (group A streptococci) |title=''Streptococcus pyogenes'': Basic Biology to Clinical Manifestations|date=October 9, 2022|orig-date=Originally published September 15, 2022| veditors = Ferretti JJ, Stevens DL, Fischetti VA|edition=2nd|publisher=University of Oklahoma Health Sciences Center|location=Oklahoma City, United States | chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK587110/|access-date=May 11, 2023|via=National Center for Biotechnology Information, National Library of Medicine |pmid=36479747}}</ref>

An estimated 700 million GAS infections occur worldwide each year. While the overall mortality rate for these infections is less than 0.1%, over 650,000 of the cases are severe and invasive, and these cases have a mortality rate of 25%.<ref>{{cite journal | vauthors = Aziz RK, Kansal R, Aronow BJ, Taylor WL, Rowe SL, Kubal M, Chhatwal GS, Walker MJ, Kotb M | display-authors = 6 | title = Microevolution of group A streptococci in vivo: capturing regulatory networks engaged in sociomicrobiology, niche adaptation, and hypervirulence | journal = PLOS ONE | volume = 5 | issue = 4 | pages = e9798 | date = April 2010 | pmid = 20418946 | pmc = 2854683 | doi = 10.1371/journal.pone.0009798 | veditors = Ahmed N | doi-access = free | bibcode = 2010PLoSO...5.9798A }}</ref> Early recognition and treatment are critical; [[Medical diagnosis|diagnostic failure]] can result in [[sepsis]] and death.<ref name=NYT71112>{{cite news|title=An Infection, Unnoticed, Turns Unstoppable|url=https://www.nytimes.com/2012/07/12/nyregion/in-rory-stauntons-fight-for-his-life-signs-that-went-unheeded.html|access-date=July 12, 2012|newspaper=The New York Times|date=July 11, 2012|author=Jim Dwyer}}</ref><ref name=NYT71812>{{cite news|title=After Boy's Death, Hospital Alters Discharging Procedures|url=https://www.nytimes.com/2012/07/19/nyregion/after-rory-stauntons-death-hospital-alters-discharge-procedures.html|access-date=July 19, 2012|newspaper=The New York Times|date=July 18, 2012|author=Jim Dwyer}}</ref> ''S. pyogenes'' is clinically and historically significant as the cause of [[scarlet fever]], which results from exposure to the species' [[exotoxin]].<ref name="pmid29939666">{{Citation | vauthors = Pardo S, Perera TB | chapter = Scarlet Fever |date=2023 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK507889/ | title = StatPearls |access-date=January 14, 2024 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29939666 }}</ref>

==Epidemiology==
[[File:Streptococcus pyogenes.jpg|thumb|Chains of ''S. pyogenes'' bacteria (orange) at 900× magnification]]
[[File:Gram stain of Streptococcus pyogenes.jpg|thumb|[[Gram stain]] of ''Streptococcus pyogenes''.]]
Unlike most bacterial pathogens, ''S. pyogenes'' only infects humans. Thus, [[Zoonosis|zoonotic transmission]] from an animal (or animal products) to a human is rare.<ref>{{cite journal | vauthors = Gera K, McIver KS | title = Laboratory growth and maintenance of Streptococcus pyogenes (the Group A Streptococcus, GAS) | journal = Current Protocols in Microbiology | volume = 30 | pages = 9D.2.1–9D.2.13 | date = October 2013 | pmid = 24510893 | pmc = 3920295 | doi = 10.1002/9780471729259.mc09d02s30 }}</ref>

''S. pyogenes'' typically colonizes the throat, genital mucosa, [[rectum]], and skin. Of healthy adults, 1% to 5% have throat, vaginal, or rectal carriage, with children being more common carriers. Most frequently, transmission from one person to another occurs due to inhalation of [[respiratory droplet]]s, produced by sneezing and coughing from an infected person. Skin contact, contact with [[Fomite|objects]] harboring the bacterium, and consumption of contaminated food are possible but uncommon modes of transmission. [[Streptococcal pharyngitis]] occurs most frequently in late winter to early spring in most countries as indoor spaces are used more often and thus more crowded. Disease cases are the lowest during autumn.<ref name="epidemiology">{{cite book| vauthors = Androulla E, Theresa L |chapter=Epidemiology of Streptococcus pyogenes |title=Streptococcus pyogenes : Basic Biology to Clinical Manifestations|date=February 10, 2016|publisher=University of Oklahoma Health Sciences Center |location=Oklahoma City, United States |chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK343616/ |access-date=February 24, 2018 |pmid=26866237 }}</ref>

Maternal ''S. pyogenes'' infection usually happens in late pregnancy, at more than 30 weeks of [[Gestational age|gestation]] to four weeks [[postpartum]]. Maternal infections account for 2 to 4% of all clinically diagnosed ''S. pyogenes'' infections.<ref name="epidemiology" /> The risk of [[sepsis]] is relatively high compared to other bacterial infections acquired during pregnancy, and ''S. pyogenes'' is a leading cause of [[septic shock]] and death in pregnant and postpartum women.<ref>{{cite journal | vauthors = Tanaka H, Katsuragi S, Hasegawa J, Tanaka K, Osato K, Nakata M, Murakoshi T, Sekizawa A, Kanayama N, Ishiwata I, Ikeda T | display-authors = 6 | title = The most common causative bacteria in maternal sepsis-related deaths in Japan were group A Streptococcus: A nationwide survey | journal = Journal of Infection and Chemotherapy | volume = 25 | issue = 1 | pages = 41–44 | date = January 2019 | pmid = 30377069 | doi = 10.1016/j.jiac.2018.10.004 }}</ref>

==Bacteriology==
[[File:Streptococcus Pyogenes (Group A Strep) (52606801786).jpg|thumb|False-color [[scanning electron microscope]] image of ''Streptococcus pyogenes'' (orange) during [[phagocytosis]] with a human [[neutrophil]] (blue)]]

=== Serotyping ===

In 1928, [[Rebecca Lancefield]] published a method for serotyping ''S. pyogenes'' based on its cell-wall polysaccharide,<ref name=Pignanelli_2015>{{cite journal | vauthors = Pignanelli S, Brusa S, Pulcrano G, Catania MR, Cocchi E, Lanari M | title = A rare case of infant sepsis due to the emm-89 genotype of Group A Streptococcus within a community-acquired cluster | journal = The New Microbiologica | volume = 38 | issue = 4 | pages = 589–592 | date = October 2015 | pmid = 26485019 }}</ref> a [[virulence]] factor displayed on its surface.<ref name=Lancefield_1928>{{cite journal | vauthors = Lancefield RC | title = The Antigenic Complex of Streptococcus Hæmolyticus | journal = The Journal of Experimental Medicine | volume = 47 | issue = 1 | pages = 91–103 | date = January 1928 | pmid = 19869404 | pmc = 2131344 | doi = 10.1084/jem.47.1.91 }}</ref> Later, in 1946, Lancefield described the serologic classification of ''S. pyogenes'' isolates based on components of their surface [[pilus|pili]] (known as the T-antigen)<ref name=Lancefield_1946>{{cite journal | vauthors = Lancefield RC, Dole VP | title = The Properties of T Antigens Extracted from Group a Hemolytic Streptococci | journal = The Journal of Experimental Medicine | volume = 84 | issue = 5 | pages = 449–471 | date = October 1946 | pmid = 19871581 | pmc = 2135665 | doi = 10.1084/jem.84.5.449 }}</ref>  which are used by bacteria to attach to host cells.<ref name=Mora_2005>{{cite journal | vauthors = Mora M, Bensi G, Capo S, Falugi F, Zingaretti C, Manetti AG, Maggi T, Taddei AR, Grandi G, Telford JL | display-authors = 6 | title = Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 43 | pages = 15641–15646 | date = October 2005 | pmid = 16223875 | pmc = 1253647 | doi = 10.1073/pnas.0507808102 | doi-access = free | bibcode = 2005PNAS..10215641M }}</ref> As of 2016, a total of 120 [[M protein (Streptococcus)|M proteins]] have been identified. These M proteins are encoded by 234 type ''emm'' genes with greater than 1,200 alleles.<ref name="epidemiology"/>

=== Lysogeny ===

All strains of ''S. pyogenes'' are polylysogenized, in that they carry one or more [[bacteriophage]] in their genomes.<ref name="Ferretti_2001">{{cite journal | vauthors = Ferretti JJ, McShan WM, Ajdic D, Savic DJ, Savic G, Lyon K, Primeaux C, Sezate S, Suvorov AN, Kenton S, Lai HS, Lin SP, Qian Y, Jia HG, Najar FZ, Ren Q, Zhu H, Song L, White J, Yuan X, Clifton SW, Roe BA, McLaughlin R | display-authors = 6 | title = Complete genome sequence of an M1 strain of Streptococcus pyogenes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 8 | pages = 4658–4663 | date = April 2001 | pmid = 11296296 | pmc = 31890 | doi = 10.1073/pnas.071559398 | doi-access = free | bibcode = 2001PNAS...98.4658F }}</ref> Some of the phages may be defective, but in some cases active phage may compensate for defects in others.<ref name="Canchaya_2002">{{cite journal | vauthors = Canchaya C, Desiere F, McShan WM, Ferretti JJ, Parkhill J, Brüssow H | title = Genome analysis of an inducible prophage and prophage remnants integrated in the Streptococcus pyogenes strain SF370 | journal = Virology | volume = 302 | issue = 2 | pages = 245–258 | date = October 2002 | pmid = 12441069 | doi = 10.1006/viro.2002.1570 | doi-access = free }}</ref> In general, the genome of ''S. pyogenes'' strains isolated during disease are >90% identical, they differ by the phage they carry.<ref name="Banks_2003">{{cite journal | vauthors = Banks DJ, Porcella SF, Barbian KD, Martin JM, Musser JM | title = Structure and distribution of an unusual chimeric genetic element encoding macrolide resistance in phylogenetically diverse clones of group A Streptococcus | journal = The Journal of Infectious Diseases | volume = 188 | issue = 12 | pages = 1898–1908 | date = December 2003 | pmid = 14673771 | doi = 10.1086/379897 | doi-access = free }}</ref>

=== 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>

{| class="wikitable" font-size:85%; margin-left:15px"
|-
!Name
!Description
|-
|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.
|-
|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.
|-
|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).
|-
|Streptococcal pyrogenic exotoxin C (SpeC)
|-
|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>
|-
|[[Streptokinase]]
|Enzymatically activates [[plasminogen]], a proteolytic enzyme, into [[plasmin]], which in turn digests [[fibrin]] and other proteins
|-
|[[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.
|-
|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>
|-
|[[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>
|-
|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"/>
|-
|}

=== Genome ===
The genomes of different strains were sequenced (genome size is 1.8–1.9 Mbp),<ref>{{cite journal | vauthors = Beres SB, Richter EW, Nagiec MJ, Sumby P, Porcella SF, DeLeo FR, Musser JM | title = Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 18 | pages = 7059–7064 | date = May 2006 | pmid = 16636287 | pmc = 1459018 | doi = 10.1073/pnas.0510279103 | doi-access = free | bibcode = 2006PNAS..103.7059B }}</ref> encoding about 1700-1900 proteins (1700 in strain NZ131,<ref>{{cite web|url=http://microbesonline.org/cgi-bin/genomeInfo.cgi?tId=471876|title=Streptococcus pyogenes NZ131}}</ref><ref name="McShan2008">{{cite journal | vauthors = McShan WM, Ferretti JJ, Karasawa T, Suvorov AN, Lin S, Qin B, Jia H, Kenton S, Najar F, Wu H, Scott J, Roe BA, Savic DJ | display-authors = 6 | title = Genome sequence of a nephritogenic and highly transformable M49 strain of Streptococcus pyogenes | journal = Journal of Bacteriology | volume = 190 | issue = 23 | pages = 7773–7785 | date = December 2008 | pmid = 18820018 | pmc = 2583620 | doi = 10.1128/JB.00672-08 }}</ref> 1865 in strain MGAS5005<ref name="Sumby">{{cite journal | vauthors = Sumby P, Porcella SF, Madrigal AG, Barbian KD, Virtaneva K, Ricklefs SM, Sturdevant DE, Graham MR, Vuopio-Varkila J, Hoe NP, Musser JM | display-authors = 6 | title = Evolutionary origin and emergence of a highly successful clone of serotype M1 group a Streptococcus involved multiple horizontal gene transfer events | journal = The Journal of Infectious Diseases | volume = 192 | issue = 5 | pages = 771–782 | date = September 2005 | pmid = 16088826 | doi = 10.1086/432514 | doi-access = free }}</ref><ref>{{cite web|url=http://microbesonline.org/cgi-bin/genomeInfo.cgi?tId=293653|title=Streptococcus pyogenes MGAS5005}}</ref>). Complete genome sequences of the type strain of ''S. pyogenes'' ([https://www.phe-culturecollections.org.uk/products/bacteria/detail.jsp?refId=NCTC+8198&collection=nctc NCTC 8198<sup>T</sup>] = [https://ccug.se/strain?id=4207&s=0&p=1&sort=rel&collection=entire&records=25&t=4207 CCUG 4207<sup>T</sup>]) are available in [[DNA Data Bank of Japan]], [[European Nucleotide Archive]], and [[GenBank]] under the accession numbers [https://www.ncbi.nlm.nih.gov/nuccore/NZ_LN831034.1 LN831034] and [https://www.ncbi.nlm.nih.gov/nuccore/NZ_CP028841.1 CP028841].<ref>{{cite journal | vauthors = Salvà-Serra F, Jaén-Luchoro D, Jakobsson HE, Gonzales-Siles L, Karlsson R, Busquets A, Gomila M, Bennasar-Figueras A, Russell JE, Fazal MA, Alexander S, Moore ER | display-authors = 6 | title = Complete genome sequences of Streptococcus pyogenes type strain reveal 100%-match between PacBio-solo and Illumina-Oxford Nanopore hybrid assemblies | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 11656 | date = July 2020 | pmid = 32669560 | pmc = 7363880 | doi = 10.1038/s41598-020-68249-y }}</ref>

=== Biofilm formation ===
[[Biofilm]]s are a way for ''S. pyogenes,'' as well as other bacterial cells, to communicate with each other. In the biofilm gene expression for multiple purposes (such as defending against the host immune system) is controlled via [[quorum sensing]].<ref name="pmid21829369">{{cite journal | vauthors = Chang JC, LaSarre B, Jimenez JC, Aggarwal C, Federle MJ | title = Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development | journal = PLOS Pathogens | volume = 7 | issue = 8 | pages = e1002190 | date = August 2011 | pmid = 21829369 | pmc = 3150281 | doi = 10.1371/journal.ppat.1002190 | doi-access = free }}</ref> One of the biofilm forming pathways in GAS is the Rgg2/3 pathway. It regulates SHP's (short hydrophobic peptides) that are quorum sensing pheromones, a.k.a. autoinducers. The SHP's are translated to an immature form of the pheromone and must undergo processing, first by a metalloprotease enzyme inside the cell and then in the extracellular space, to reach their mature active form. The mode of transportation out of the cell and the extracellular processing factor(s) are still unknown. The mature SHP pheromone can then be taken into nearby cells and the cell it originated from via a transmembrane protein, oligopeptide permease.<ref name="pmid21829369"/> In the cytosol the pheromones have two functions in the Rgg2/3 pathway. Firstly, they inhibit the activity of Rgg3 which is a transcriptional regulator repressing SHP production. Secondly, they bind another transcriptional regulator, Rgg2, that increases the production of SHP's, having an antagonistic effect to Rgg3. SHP's activating their own transcriptional activator creates a positive feedback loop, which is common for the production for quorum sensing peptides. It enables the rapid production of the pheromones in large quantities. The production of SHP's increases biofilm biogenesis.<ref name="pmid21829369"/> It has been suggested that GAS switches between biofilm formation and degradation by utilizing pathways with opposing effects. Whilst Rgg2/3 pathway increases biofilm, the [[RopB]] pathway disrupts it. RopB is another Rgg-like protein (Rgg1) that directly activates SpeB (streptococcal pyrogenic exotoxin B), a cysteine protease that acts as a virulence factor. In the absence of this pathway, biofilm formation is enhanced, possibly due to the lack of the protease degrading pheromones or other Rgg2/3 pathway counteracting effects.<ref name="pmid21829369"/>

== Disease ==
{{See also|Group A streptococcal infection}}

''S. pyogenes'' is the cause of many human diseases, ranging from mild superficial skin infections to life-threatening systemic diseases.<ref name=Sherris/> The most frequent manifestations of disease are commonly known as [[scarlet fever]]. Infections typically begin in the throat or skin. The most striking sign is a strawberry-like rash. Examples of mild ''S. pyogenes'' infections include [[Streptococcal pharyngitis|pharyngitis]] (strep throat) and localized skin infection ([[impetigo]]). [[Erysipelas]] and [[cellulitis]] are characterized by multiplication and lateral spread of ''S. pyogenes'' in deep layers of the skin. ''S. pyogenes'' invasion and multiplication in the [[fascia]] beneath the skin can lead to [[necrotizing fasciitis]], a life-threatening surgical emergency.<ref>{{cite journal | vauthors = Schroeder JL, Steinke EE | title = Necrotizing fasciitis--the importance of early diagnosis and debridement | journal = AORN Journal | volume = 82 | issue = 6 | pages = 1031–1040 | date = December 2005 | pmid = 16478083 | doi = 10.1016/s0001-2092(06)60255-x }}</ref><ref>
{{cite web |url=https://www.cdc.gov/Features/NecrotizingFasciitis/
 |title=Necrotizing Fasciitis |author=<!--Not stated--> |date=October 26, 2017 |website=CDC |publisher=Content source: National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases. Page maintained by: Office of the Associate Director for Communication, Digital Media Branch, Division of Public Affairs |access-date=January 6, 2018  }}
</ref> The bacterium is also an important cause of [[neonatal infection|infection in newborn]]s, who are susceptible to some forms of the infection that are rarely seen in adults, including [[meningitis]].<ref name="BaucellsMercadal Hally2015">{{cite journal | vauthors = Baucells BJ, Mercadal Hally M, Álvarez Sánchez AT, Figueras Aloy J | title = Asociaciones de probióticos para la prevención de la enterocolitis necrosante y la reducción de la sepsis tardía y la mortalidad neonatal en recién nacidos pretérmino de menos de 1.500g: una revisión sistemática | trans-title = Probiotic associations in the prevention of necrotising enterocolitis and the reduction of late-onset sepsis and neonatal mortality in preterm infants under 1,500g: A systematic review | journal = Anales de Pediatria | language = Spanish | volume = 85 | issue = 5 | pages = 247–255 | date = November 2016 | pmid = 26611880 | doi = 10.1016/j.anpedi.2015.07.038 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Berner R, Herdeg S, Gordjani N, Brandis M | title = Streptococcus pyogenes meningitis: report of a case and review of the literature | journal = European Journal of Pediatrics | volume = 159 | issue = 7 | pages = 527–529 | date = July 2000 | doi = 10.1007/s004310051325 | pmid = 10923229 | s2cid = 7693087 }}</ref>

Like many pathogenic bacteria, ''S. pyogenes'' may colonize a healthy person's respiratory system without causing disease, existing as a [[commensal]] member of the respiratory microbiota. It is commonly found in some populations as part of the mixed [[Human microbiome|microbiome]] of the upper respiratory tract. Individuals who have the bacterium in their bodies but no signs of disease are known as [[asymptomatic carrier]]s.<ref name="pmid38360357">{{cite journal |vauthors=Hung TY, Phuong LK, Grobler A, Tong SY, Freeth P, Pelenda A, Gibney KB, Steer AC |title=Antibiotics to eradicate Streptococcus pyogenes pharyngeal carriage in asymptomatic children and adults: A systematic review |journal=J Infect |volume=88 |issue=3 |pages=106104 |date=March 2024 |pmid=38360357 |doi=10.1016/j.jinf.2024.01.003 |url=|doi-access=free }}</ref><ref name="pmid31200755"/><ref name="pmid29554121"/> The bacteria may start to cause disease when the host's immune system weakens, such as during a viral respiratory infection, which may lead to ''S. pyogenes'' [[superinfection]].<ref name="pmid31200755">{{cite journal | vauthors = Othman AM, Assayaghi RM, Al-Shami HZ, Saif-Ali R | title = Asymptomatic carriage of Streptococcus pyogenes among school children in Sana'a city, Yemen | journal = BMC Research Notes | volume = 12 | issue = 1 | pages = 339 | date = June 2019 | pmid = 31200755 | pmc = 6570875 | doi = 10.1186/s13104-019-4370-5 | doi-access = free }}</ref><ref name="pmid29554121">{{cite journal | vauthors = Oliver J, Malliya Wadu E, Pierse N, Moreland NJ, Williamson DA, Baker MG | title = Group A Streptococcus pharyngitis and pharyngeal carriage: A meta-analysis | journal = PLOS Neglected Tropical Diseases | volume = 12 | issue = 3 | pages = e0006335 | date = March 2018 | pmid = 29554121 | pmc = 5875889 | doi = 10.1371/journal.pntd.0006335 | doi-access = free }}</ref>

''S. pyogenes'' infections are commonly associated with the release of one or more bacterial [[toxin]]s. The release of endotoxins from throat infections has been linked to the development of scarlet fever.<ref name="pmid29939666" /> Other toxins produced by ''S. pyogenes'' may lead to streptococcal [[toxic shock syndrome]], a life-threatening emergency.<ref name=Sherris/>

''S. pyogenes'' can also cause disease in the form of post-infectious "non-pyogenic" (not associated with local bacterial multiplication and pus formation) syndromes. These [[autoimmune]]-mediated complications follow a small percentage of infections and include [[rheumatic fever]] and acute [[post-infectious glomerulonephritis]]. Both conditions appear several weeks following the initial streptococcal infection. Rheumatic fever is characterized by inflammation of the joints and/or heart following an episode of [[streptococcal pharyngitis]]. Acute glomerulonephritis, inflammation of the [[renal glomerulus]], can follow streptococcal pharyngitis or skin infection.{{citation needed|date=February 2023}}

''S. pyogenes'' is sensitive to [[penicillin]], and has not developed [[Antimicrobial resistance|resistance]] to it,<ref>{{Cite journal |last=Horn |first=D. L. |last2=Zabriskie |first2=J. B. |last3=Austrian |first3=R. |last4=Cleary |first4=P. P. |last5=Ferretti |first5=J. J. |last6=Fischetti |first6=V. A. |last7=Gotschlich |first7=E. |last8=Kaplan |first8=E. L. |last9=McCarty |first9=M. |last10=Opal |first10=S. M. |last11=Roberts |first11=R. B. |last12=Tomasz |first12=A. |last13=Wachtfogel |first13=Y. |date=June 1998 |title=Why have group A streptococci remained susceptible to penicillin? Report on a symposium |url=https://pubmed.ncbi.nlm.nih.gov/9636860/ |journal=Clinical Infectious Diseases|volume=26 |issue=6 |pages=1341–1345 |doi=10.1086/516375 |issn=1058-4838 |pmid=9636860}}</ref> making penicillin a suitable [[antibiotic]] to treat infections caused by this bacterium. Failure of treatment with penicillin is generally attributed to other local commensal microorganisms producing [[β-lactamase]], or failure to achieve adequate tissue levels in the pharynx. Certain strains have developed resistance to [[macrolides]], [[tetracyclines]], and [[clindamycin]].<ref>{{cite journal |author = Tadesse, Molla |title = Prevalence, Antibiotic Susceptibility Profile and Associated Factors of Group A Streptococcal pharyngitis Among Pediatric Patients with Acute Pharyngitis in Gondar, Northwest Ethiopia |date = March 2023 |journal = Infection and Drug Resistance|volume = 16 |pages = 1637–1648 |doi = 10.2147/IDR.S402292 |doi-access = free |pmid = 36992964 |pmc = 0040342}}</ref>

== Vaccine ==
There is a polyvalent inactivated vaccine against several types of ''Streptococcus'' including ''S. pyogenes'' called "vacuna antipiogena polivalente BIOL". It is recommended to be administered in a 5 week series. Two weekly applications are made at intervals of 2 to 4 days. The vaccine is produced by the Instituto Biológico Argentino.<ref>{{cite web|url=https://biol.com.ar/uploads/filemanager/Vacuna%20Antipiogena%20Biol.pdf |archive-url=https://ghostarchive.org/archive/20221010/https://biol.com.ar/uploads/filemanager/Vacuna%20Antipiogena%20Biol.pdf |archive-date=October 10, 2022 |url-status=live|title=Package leaflet on BIOL official website}}</ref>

There is another potential vaccine being developed; the vaccine candidate peptide is called StreptInCor.<ref>{{cite journal | vauthors = Guilherme L, Ferreira FM, Köhler KF, Postol E, Kalil J | title = A vaccine against Streptococcus pyogenes: the potential to prevent rheumatic fever and rheumatic heart disease | journal = American Journal of Cardiovascular Drugs | volume = 13 | issue = 1 | pages = 1–4 | date = February 2013 | pmid = 23355360 | doi = 10.1007/s40256-013-0005-8 | s2cid = 13071864 | doi-access = free }}</ref>

== Applications ==
=== Bionanotechnology ===
Many ''S. pyogenes'' proteins have unique properties, which have been harnessed in recent years to produce a highly specific "superglue"<ref name="pmid28550142">{{cite journal | vauthors = Howarth M | title = Smart superglue in streptococci? The proof is in the pulling | journal = The Journal of Biological Chemistry | volume = 292 | issue = 21 | pages = 8998–8999 | date = May 2017 | pmid = 28550142 | pmc = 5448131 | doi = 10.1074/jbc.H117.777466 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zakeri B, Fierer JO, Celik E, Chittock EC, Schwarz-Linek U, Moy VT, Howarth M | title = Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 12 | pages = E690–E697 | date = March 2012 | pmid = 22366317 | pmc = 3311370 | doi = 10.1073/pnas.1115485109 | doi-access = free | bibcode = 2012PNAS..109E.690Z }}</ref> and a route to enhance the effectiveness of [[antibody therapy (disambiguation)|antibody therapy]].<ref>{{cite journal | vauthors = Baruah K, Bowden TA, Krishna BA, Dwek RA, Crispin M, Scanlan CN | title = Selective deactivation of serum IgG: a general strategy for the enhancement of monoclonal antibody receptor interactions | journal = Journal of Molecular Biology | volume = 420 | issue = 1–2 | pages = 1–7 | date = June 2012 | pmid = 22484364 | pmc = 3437440 | doi = 10.1016/j.jmb.2012.04.002 }}</ref>

=== Genome editing ===
The [[CRISPR]] system from this organism<ref name="Deltcheva2011">{{cite journal | vauthors = Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E | display-authors = 6 | title = CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III | journal = Nature | volume = 471 | issue = 7340 | pages = 602–607 | date = March 2011 | pmid = 21455174 | pmc = 3070239 | doi = 10.1038/nature09886 | bibcode = 2011Natur.471..602D }}</ref> that is used to recognize and destroy [[DNA]] from invading viruses, thus stopping the infection, was appropriated in 2012 for use as a genome-editing tool that could potentially alter any piece of DNA and later [[RNA]].<ref>{{Cite news|url=https://www.nytimes.com/2016/06/04/science/rna-c2c2-gene-editing-dna-crispr.html|title=Scientists Find Form of Crispr Gene Editing With New Capabilities| vauthors = Zimmer C |date=June 3, 2016|newspaper=The New York Times|issn=0362-4331|access-date=June 10, 2016}}</ref>

== See also ==
* [[Friedrich Fehleisen]]
* [[Friedrich Julius Rosenbach]]
* [[Friedrich Loeffler]]
* [[Frederick Twort]]

== References ==
{{Reflist|32em}}

== Further reading ==
{{Refbegin|35em}}
* {{cite journal | vauthors = Freiberg JA, McIver KS, Shirtliff ME | title = In vivo expression of Streptococcus pyogenes immunogenic proteins during tibial foreign body infection | journal = Infection and Immunity | volume = 82 | issue = 9 | pages = 3891–3899 | date = September 2014 | pmid = 25001603 | pmc = 4187806 | doi = 10.1128/IAI.01831-14 }}
* {{cite book |author=Rosenbach FJ |title=Mikro-Organismen bei den Wund-Infections-Krankheiten des Menschen |ol=22886502M |language=de |publisher=J.F. Bergmann |year=1884 |url=https://archive.org/details/mikroorganismenb00roseuoft }}
* {{cite journal | vauthors = Wilson LG | title = The early recognition of streptococci as causes of disease | journal = Medical History | volume = 31 | issue = 4 | pages = 403–414 | date = October 1987 | pmid = 3316876 | pmc = 1139783 | doi = 10.1017/s0025727300047268 }}
* {{cite journal | vauthors = Rolleston JD | title = The History of Scarlet Fever | journal = British Medical Journal | volume = 2 | issue = 3542 | pages = 926–929 | date = November 1928 | pmid = 20774279 | pmc = 2456687 | doi = 10.1136/bmj.2.3542.926 }}
* {{cite web |url=https://www.who.int/child_adolescent_health/documents/fch_cah_05_07/en/index.html |archive-url=https://web.archive.org/web/20080312100548/http://www.who.int/child_adolescent_health/documents/fch_cah_05_07/en/index.html |url-status=dead |archive-date=March 12, 2008 |author=World Health Organization |title=The current evidence for the burden of group A streptococcal diseases |year=2005 |format=PDF |access-date=August 22, 2011}}
* {{cite journal | vauthors = Carapetis JR, Steer AC, Mulholland EK, Weber M | title = The global burden of group A streptococcal diseases | journal = The Lancet. Infectious Diseases | volume = 5 | issue = 11 | pages = 685–694 | date = November 2005 | pmid = 16253886 | doi = 10.1016/S1473-3099(05)70267-X }} (corresponding summary article)
{{Refend}}
* {{cite book |title=Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]  |publisher=University of Oklahoma Health Sciences Center |location= Oklahoma City, OK |year=2016 |pmid=26866208 |url= https://www.ncbi.nlm.nih.gov/books/NBK333424/ | vauthors = Ferretti JJ, Stevens DL, Fischetti VA }}
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== External links ==
* [http://bacdive.dsmz.de/index.php?search=14758&submit=Search Type strain of ''Streptococcus pyogenes'' at Bac''Dive'' -  the Bacterial Diversity Metadatabase]
* [https://scitechdaily.com/nature-inspired-crispr-enzyme-discoveries-vastly-expand-genome-editing/ Nature-Inspired CRISPR Enzyme Discoveries Vastly Expand Genome Editing ]. On: SciTechDaily. June 16, 2020. Source: Media Lab, Massachusetts Institute of Technology.

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{{DEFAULTSORT:Streptococcus Pyogenes}}
[[Category:Streptococcaceae]]
[[Category:Gram-positive bacteria]]
[[Category:Pathogenic bacteria]]
[[Category:Scarlet fever]]
[[Category:Tonsil disorders]]
[[Category:Bacteria described in 1884]]