Journal article
Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
S Brouwer, TC Barnett, D Ly, KJ Kasper, DMP De Oliveira, T Rivera-Hernandez, AJ Cork, L McIntyre, MG Jespersen, J Richter, BL Schulz, G Dougan, V Nizet, KY Yuen, Y You, JK McCormick, ML Sanderson-Smith, MR Davies, MJ Walker
Nature Communications | NATURE PORTFOLIO | Published : 2020
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 bacteri..
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Awarded by National Institutes of Health
Funding Acknowledgements
We kindly acknowledge James McCluskey (University of Melbourne, Melbourne, Australia) for providing HLA-B6 mice transgenic for human CD4 and HLA-DR4-DQ8 genes; Luke McAlary (University of Wollongong, Wollongong, Australia) for assistance with microscopy; and assistance from the sequencing and pathogen informatics core teams at The Wellcome Trust Sanger Institute (Hinxton, UK). We thank Thomas Proft, Mitchell Acev, Heema Vyas, and Jason McArthur for providing genetic constructs. This work was supported by grants from the National Health and Medical Research Council of Australia, the Illawarra Health and Medical Research Institute, the Sanming Project of Medicine in Shenzhen, China (SZSM201911014), The Wellcome Trust, UK, the National Institutes of Health, USA, and the Canadian Institutes of Health Research.