Identification of Three Novel Superantigen-Encoding Genes in Streptococcus equi subsp. zooepidemicus , szeF , szeN , and szeP

Abstract

The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel superantigen-encoding genes. The products of szeF, szeN, and szeP share 59%, 49%, and 34% amino acid sequence identity with SPEH, SPEM, and SPEL, respectively. Recombinant SzeF, SzeN, and SzeP stimulated the proliferation of equine peripheral blood mononuclear cells, and tumor necrosis factor alpha (TNF-␣) and gamma interferon (IFN-␥) production, in vitro. Although none of these superantigen genes were encoded within functional prophage elements, szeN and szeP were located next to a prophage remnant, suggesting that they were acquired by horizontal transfer. Eighty-one of 165 diverse S. equi subsp. zooepidemicus strains screened, including 7 out of 15 isolates from cases of disease in humans, contained at least one of these new superantigen-encoding genes. The presence of szeN or szeP, but not szeF, was significantly associated with mitogenic activity in the S. equi subsp. zooepidemicus population (P < 0.000001, P < 0.000001, and P ‫؍‬ 0.104, respectively). We conclude that horizontal transfer of these novel superantigens from and within the diverse S. equi subsp. zooepidemicus population is likely to have implications for veterinary and human disease.

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

“…Gene gain via the horizontal acquisition of mobile genetic elements is a key factor in the emergence of new pathogenic strains of streptococci. For example, acquisition of superantigen-encoding genes by S. pyogenes has been associated with increased morbidity and mortality in humans (39,40). The emergence of a new, epidemic ST of S. suis during the Chinese outbreak leading to unusual clinical manifestations related to STSLS allowed the hypothesis of the acquisition of superantigens by this important zoonotic pathogen to arise as well.…”

Staphylococcal and Streptococcal Superantigen Exotoxins

“…In fact, a number of other organisms produce superantigens. Recent reports of coagulasenegative staphylococci of animal origin (40,41) and other betahemolytic streptococci, namely, groups B, C, and G (4,8,15,25,31,33,(74)(75)(76), have been published. Superantigens of group B streptococci have not been purified.…”

Clones of Streptococcus zooepidemicus from Outbreaks of Hemorrhagic Canine Pneumonia and Associated Immune Responses

“…Based on MLST, SzP, and SzM analyses (Table 1), the S. zooepidemicus clones responsible for each of the US outbreaks were different from each other and from BHS5, a United Kingdom isolate (14). S. zooepidemicus strains 985 and BHS5 have been reported to be closely related, yet their SzM sequences show low levels of identity (14). Moreover, the szeF sequence found in S. zooepidemicus strain BHS5 is missing from S. zooepidemicus strain 985.…”

“…Only one isolate was submitted from each of 2 separate outbreaks among greyhounds in Texas in 1992 and 1993. Based on MLST, SzP, and SzM analyses (Table 1), the S. zooepidemicus clones responsible for each of the US outbreaks were different from each other and from BHS5, a United Kingdom isolate (14). S. zooepidemicus strains 985 and BHS5 have been reported to be closely related, yet their SzM sequences show low levels of identity (14).…”

“…Comparison of the SzM sequences of isolates from each outbreak with the SzM sequence of S. zooepidemicus strain BHS5 isolated in the United Kingdom revealed identities that ranged from 23.92 to 57.37%. The BHS5 strain was chosen for identity comparisons because of access to its genomic sequence (14). Interestingly, although its sequence type (ST-123) included 6 loci common to isolates 985 and 997 (ST-129) from greyhounds from the outbreak in Kansas in 2005, the SzP and SzM sequences of these isolates were not shared.…”