| First Author | Brouwer S | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 5018 |
| PubMed ID | 33024089 | Mgi Jnum | J:298733 |
| Mgi Id | MGI:6470325 | Doi | 10.1038/s41467-020-18700-5 |
| Citation | Brouwer S, et al. (2020) Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes. Nat Commun 11(1):5018 |
| abstractText | The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage PhiHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of PhiHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the PhiHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage PhiHKU.vir exotoxins. |
