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

Stephan Brouwer, Timothy C. Barnett, Diane Ly, Katherine J. Kasper, David M. P. Oliveira, Tania Rivera-Hernandez, Amanda J. Cork, Liam McIntyre, Magnus G. Jespersen, Johanna Richter, Benjamin L. Schulz, Gordon Dougan, Victor Nizet, Kwok-Yung Yuen, Yuanhai You, John K. McCormick, Martina L. Sanderson-Smith, Mark R. Davies and Mark J. Walker ()
Additional contact information
Stephan Brouwer: The University of Queensland
Timothy C. Barnett: The University of Queensland
Diane Ly: Illawarra Health and Medical Research Institute
Katherine J. Kasper: Western University
David M. P. Oliveira: The University of Queensland
Tania Rivera-Hernandez: The University of Queensland
Amanda J. Cork: The University of Queensland
Liam McIntyre: The University of Melbourne
Magnus G. Jespersen: The University of Melbourne
Johanna Richter: The University of Queensland
Benjamin L. Schulz: The University of Queensland
Gordon Dougan: The Wellcome Trust Sanger Institute
Victor Nizet: University of California San Diego
Kwok-Yung Yuen: The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region
Yuanhai You: Chinese Centre for Disease Control and Prevention
John K. McCormick: Western University
Martina L. Sanderson-Smith: Illawarra Health and Medical Research Institute
Mark R. Davies: The University of Queensland
Mark J. Walker: The University of Queensland

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18700-5

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