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===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 = 761β780|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=215β241 |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=6509β6511 |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=144β150 |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=161β168 |pmid=1753942 |doi=10.1007/BF00293833 }}</ref>
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