Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

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    Author
    Brouwer, S; Barnett, TC; Ly, D; Kasper, KJ; De Oliveira, DMP; Rivera-Hernandez, T; Cork, AJ; McIntyre, L; Jespersen, MG; Richter, J; ...
    Date
    2020-10-06
    Source Title
    Nature Communications
    Publisher
    NATURE RESEARCH
    University of Melbourne Author/s
    Dougan, Gordon; Davies, Mark
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Brouwer, S., Barnett, T. C., Ly, D., Kasper, K. J., De Oliveira, D. M. P., Rivera-Hernandez, T., Cork, A. J., McIntyre, L., Jespersen, M. G., Richter, J., Schulz, B. L., Dougan, G., Nizet, V., Yuen, K. -Y., You, Y., McCormick, J. K., Sanderson-Smith, M. L., Davies, M. R. & Walker, M. J. (2020). Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes. NATURE COMMUNICATIONS, 11 (1), https://doi.org/10.1038/s41467-020-18700-5.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251666
    DOI
    10.1038/s41467-020-18700-5
    Abstract
    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 ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.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 ΦHKU.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 ΦHKU.vir exotoxins.

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