Bacteriophage T12 is a bacteriophage that infects Streptococcus pyogenes bacteria. It is a proposed species of the family Siphoviridae in the order Caudovirales also known as tailed viruses. It converts a harmless strain of bacteria into a virulent strain. It carries the speA gene which codes for erythrogenic toxin A. speA is also known as streptococcal pyogenic exotoxin A, scarlet fever toxin A, or even scarlatinal toxin. Note that the name of the gene "speA" is italicized; the name of the toxin "speA" is not italicized. Erythrogenic toxin A converts a harmless, non-virulent strain of Streptococcus pyogenes to a virulent strain through lysogeny, a life cycle which is characterized by the ability of the genome to become a part of the host cell and be stably maintained there for generations. Phages with a lysogenic life cycle are also called temperate phages. Bacteriophage T12, proposed member of family Siphoviridae including related speA-carrying bacteriophages, is also a prototypic phage for all the speA-carrying phages of Streptococcus pyogenes, meaning that its genome is the prototype for the genomes of all such phages of S. pyogenes. It is the main suspect as the cause of scarlet fever, an infectious disease that affects small children.
Discovery and further research
The possibility of bacteriophage involvement in speA production was first introduced in 1926 when Cantacuzene and Boncieu reported that nonvirulent strains of S. pyogenes were transformed to virulent strains through some transferable element. Frobisher and Brown reported similar results in 1927, and in 1949, the reports were confirmed by Bingel Later, in 1964, Zabriskie reported that phage T12 could cause speA production by lysogeny in strains that it became a part of. In 1980, Johnson, Schlievert and Watson were able to confirm this and show that the gene for speA production was transferred from toxigenic strains of bacteria to non-toxigenic strains through lysogeny. In their experiment, every transformed, toxin-producing bacterial colony was lysogenic, i.e. contained the T12 gene. In addition, none of the colonies containing the T12 genome was negative for speA, and therefore, the conclusion was drawn that all lysogens produced the toxin. However, McKane and Ferretti reported in 1981 that a spontaneous mutant of phage T12 induced speA production virulently. This mutant, the bacteriophage T12cp1, entered the lytic cycle, a life cycle in which the host cell is destroyed. In 1983, Johnson and Schlievert published a map of the T12 genome, revealing also that three rounds of packaging occur in the genome. The very next year, Johnson and Schlievert and Weeks and Ferreti also found, independently, that the bacteriophage T12 carries the structural gene for speA. In 1986, Johnson, Tomai and Schlievert mapped the attachment site (attP) for T12 adjacent to the speA gene, and established that all bacterial strains producing the toxin carry either phage T12 itself, or a closely related bacteriophage. And finally, in 1997, McShan and Ferretti published that they had found the second attachment site (attR) for T12, while also revealing in another publication, which was also credited to Tang, that bacteriophage T12 inserts into a gene that encodes a serine tRNA in the host.
Genome
The physical map of the T12 genome was found to be circular with a total length of 36.0kb. The phage genome is reported to carry the speA gene, which is a 1.7kb segment of the phage T12 genome flanked by SalI and HindIII sites.
The phage integrase gene (int) and the phage attachment site (attp) are located just upstream of the speA gene in the phage genome. The bacteriophage T12 integrates into S. pyogenes chromosome by site-specific recombination into the anticodon loop of a gene that codes for serine tRNA. The bacterial attachment site (attB) has a 96 base pair sequence homologous to the phage attachment site and is located at the 3’ end of the tRNA gene such that the coding sequence of the tRNA gene remains intact after integration of the prophage. Phage T12 is the first example of a phage from a gram-positive, low G-C content host that uses this kind of integration site.
Role in pathogenesis
Diseases like scarlet fever and Streptococcal toxic shock syndrome are caused by lysogenized streptococcal strains that produce speA. The diseases are systemic responses to the speA circulating within the body.
Scarlet fever
Scarlet fever, also known as scarletina, is so called because of the characteristic bright red rash it causes. It is most common in children between four and eight years of age.