Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
Authors
Brouwer, Stephan
Ly, Diane
Kasper, Katherine J.
Rivera-Hernandez, Tania
Cork, Amanda J.
McIntyre, Liam
Richter, Johanna
Schulz, Benjamin L.
Dougan, Gordon
You, Yuanhai
Publication Date
2020-10-06Journal Title
Nature Communications
Publisher
Nature Publishing Group UK
Volume
11
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Brouwer, S., Barnett, T. C., Ly, D., Kasper, K. J., De Oliveira, D. M. P., Rivera-Hernandez, T., Cork, A. J., et al. (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
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.
Keywords
Article, /631/326/1320, /692/420/254, /13/1, /13/106, /14/34, /14/63, /38/1, /38/22, /38/91, /38/39, /38/77, /38/70, /64/110, /82/80, /82/83, /82/29, article
Sponsorship
Department of Health | National Health and Medical Research Council (NHMRC) (1126805)
Identifiers
s41467-020-18700-5, 18700
External DOI: https://doi.org/10.1038/s41467-020-18700-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311142
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/