Editing Scarlet fever (section)

==Pathophysiology==
[[File:Streptococcus pyogenes.jpg|thumb|''[[Streptococcus pyogenes]]'']]

The rash of scarlet fever, which is what differentiates this disease from an isolated group A strep pharyngitis (or strep throat), is caused by specific strains of group A streptococcus that produce a [[streptococcal pyrogenic exotoxin]],<ref name="Nelson2016" /> which is mainly responsible for the skin manifestation of the infection.<ref>{{Citation |last1=Pardo |first1=Salvatore |title=Scarlet Fever |date=2022 |url=http://www.ncbi.nlm.nih.gov/books/NBK507889/ |work=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29939666 |access-date=2022-03-23 |last2=Perera |first2=Thomas B. |archive-date=6 February 2021 |archive-url=https://web.archive.org/web/20210206194418/https://www.ncbi.nlm.nih.gov/books/NBK507889/ |url-status=live }}</ref> These toxin-producing strains cause scarlet fever in people who do not already have antitoxin [[Antibody|antibodies]]. Streptococcal pyrogenic exotoxins – SPEs A, B, C. and F have been identified. The pyrogenic exotoxins, also called ''erythrogenic toxins'', cause the [[erythema]]tous rash of scarlet fever.<ref name="Medscape2021">{{cite web |title=Group A Streptococcal (GAS) Infections: Background, Pathophysiology, Etiology |url=https://emedicine.medscape.com/article/228936-overview#a3 |access-date=23 December 2022 |date=17 October 2021 |archive-date=22 February 2011 |archive-url=https://web.archive.org/web/20110222015141/http://emedicine.medscape.com/article/228936-diagnosis#a3 |url-status=live }}</ref><ref name="Nelson2016" /> The strains of group A streptococcus that cause scarlet fever need specific bacteriophages for there to be pyrogenic exotoxin production. Specifically, [[bacteriophage T12]] is responsible for the production of speA.<ref>{{Cite journal|last=McShan|first=W. Michael|date=February 1997|title=Bacteriophage T12 of Streptococcus pyogenes integrates into the gene encoding a serine tRNA|journal=Molecular Microbiology|volume=23|issue=4|pages=719–728|pmid=9157243|doi=10.1046/j.1365-2958.1997.2591616.x|s2cid=32598700|doi-access=free}}</ref> Streptococcal Pyrogenic Exotoxin A, speA, is the one most commonly associated with cases of scarlet fever that are complicated by the immune-mediated sequelae of acute rheumatic fever and post-streptococcal glomerulonephritis.<ref name="Goldsmith-2012"/>

These toxins are also known as "[[superantigen]]s" because they can cause an extensive immune response by activating some of the cells that are mainly responsible for the person's immune system.<ref name=Marks2013>{{Cite book|title=Lookingbill and Marks' Principles and Dermatology, Fifth Edition|last1=Marks|first1=James|last2=Miller|first2=Jeffrey|publisher=Elsevier|year=2013|pages=183–195}}</ref> Although the body responds to the toxins it encounters by making antibodies, those antibodies will only protect against that particular subset of toxins. They will not necessarily completely protect a person from future group A streptococcal infections, because there are 12 different pyrogenic exotoxins that may be produced by the disease, and future infections may produce a different subset of those toxins.<ref name="Nelson2016" />

===Microbiology===
The disease is caused by secretion of [[pyrogen (fever)|pyrogenic]] exotoxins by the infecting ''Streptococcus'' bacteria.<ref name="Zabriskie1964">{{cite journal |last = Zabriskie|first = J. B.|year = 1964|title = The role of temperate bacteriophage in the production of erythrogenic toxin by Group A ''Streptococci''|journal = [[Journal of Experimental Medicine]]|volume = 119|issue = 5|pages = 761–780|doi = 10.1084/jem.119.5.761|pmc = 2137738|pmid = 14157029}}{{Open access}}</ref><ref name="Krause2002">{{cite journal |last=Krause |first=R. M. |year=2002 |title=A Half-century of Streptococcal Research: Then & Now |journal=[[Indian Journal of Medical Research]] |volume=115 |pages=215–241 |pmid=12440194 }}</ref> [[Erythrogenic toxin|Streptococcal pyrogenic exotoxin A]] (''speA'') is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates into the streptococcal genome from where the toxin is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome.<ref name="McShan1997">{{cite journal |last1=McShan |first1=W. M. |last2=Ferretti |first2=J. J. |year=1997 |title=Genetic diversity in temperate bacteriophages of ''Streptococcus pyogenes'': identification of a second attachment site for phages carrying the erythrogenic toxin A gene |journal=Journal of Bacteriology |volume=179 |issue=20 |pages=6509–6511 |doi= 10.1128/jb.179.20.6509-6511.1997|pmc=179571 |pmid=9335304}}</ref>

The T12 virus itself has not been placed into a taxon by the [[International Committee on Taxonomy of Viruses]]. It has a double-stranded DNA genome and on morphological grounds appears to be a member of the ''[[Siphoviridae]].''<ref>{{cite web |title=Taxonomy browser (Streptococcus phage T12) |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=35344 |website=www.ncbi.nlm.nih.gov |publisher=National Library of Medicine (National Center for Biotechnology Information) |access-date=22 May 2022 |archive-date=22 May 2022 |archive-url=https://web.archive.org/web/20220522065103/https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=35344 |url-status=live }}</ref>

The ''speA'' gene was cloned and sequenced in 1986.<ref name="Weeks1986">{{cite journal |last1=Weeks |first1=C. R. |last2=Ferretti |first2=J. J. |year=1986 |title=Nucleotide sequence of the type A streptococcal exotoxin (erythrogenic toxin) gene from ''Streptococcus pyogenes'' bacteriophage T12 |journal=Infection and Immunity |volume=52 |issue=1 |pages=144–150 |doi= 10.1128/IAI.52.1.144-150.1986|pmid=3514452 |pmc=262210}}</ref> It is 753 base pairs in length and encodes a 29.244 [[Dalton (unit)|kilodalton]] (kDa) [[protein]]. The protein contains a putative 30-amino-acid [[signal peptide]]; removal of the signal sequence gives a predicted molecular weight of 25.787 kDa for the secreted protein. Both a promoter and a ribosome binding site ([[Shine-Dalgarno sequence]]) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination [[codon]]. The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of ''[[Staphylococcus aureus]]'' [[Enterotoxin type B|enterotoxins B]] and C1.{{citation needed|date=June 2021}}

Streptococcal phages other than T12 may also carry the ''speA'' gene.<ref name="Yu1991">{{cite journal |last1=Yu |first1=C. E. |last2=Ferretti |first2=J. J. |s2cid=36197596 |year=1991 |title=Molecular characterization of new group A streptococcal bacteriophages containing the gene for streptococcal erythrogenic toxin A (''speA'') |journal=Molecular and General Genetics |volume=231 |issue=1 |pages=161–168 |pmid=1753942 |doi=10.1007/BF00293833 }}</ref>