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

Journal Article


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Abstract


  • © 2020, The Author(s). 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.

Authors


  •   Brouwer, Stephan (external author)
  •   Barnett, Timothy C. (external author)
  •   Ly, Diane T. (external author)
  •   Kasper, Katherine (external author)
  •   De Oliveira, David (external author)
  •   Rivera-Hernandez, Tania (external author)
  •   Cork, Amanda J. (external author)
  •   McIntyre, Liam (external author)
  •   Jespersen, Magnus (external author)
  •   Richter, Johanna (external author)
  •   Schulz, Benjamin (external author)
  •   Dougan, Gordon (external author)
  •   Nizet, Victor (external author)
  •   Yuen, Kwok (external author)
  •   You, Yuanhai (external author)
  •   McCormick, John M.
  •   Sanderson-Smith, Martina L.
  •   Davies, Mark (external author)
  •   Walker, Mark (external author)

Publication Date


  • 2020

Citation


  • Brouwer, S., Barnett, T., Ly, D., Kasper, K., De Oliveira, D., Rivera-Hernandez, T., Cork, A., McIntyre, L., Jespersen, M., Richter, J., Schulz, B., Dougan, G., Nizet, V., Yuen, K., You, Y., McCormick, J., Sanderson-Smith, M., Davies, M. & Walker, M. (2020). Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes. Nature Communications, 11 (1),

Scopus Eid


  • 2-s2.0-85091976357

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2579&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1551

Volume


  • 11

Issue


  • 1

Place Of Publication


  • United Kingdom

Abstract


  • © 2020, The Author(s). 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.

Authors


  •   Brouwer, Stephan (external author)
  •   Barnett, Timothy C. (external author)
  •   Ly, Diane T. (external author)
  •   Kasper, Katherine (external author)
  •   De Oliveira, David (external author)
  •   Rivera-Hernandez, Tania (external author)
  •   Cork, Amanda J. (external author)
  •   McIntyre, Liam (external author)
  •   Jespersen, Magnus (external author)
  •   Richter, Johanna (external author)
  •   Schulz, Benjamin (external author)
  •   Dougan, Gordon (external author)
  •   Nizet, Victor (external author)
  •   Yuen, Kwok (external author)
  •   You, Yuanhai (external author)
  •   McCormick, John M.
  •   Sanderson-Smith, Martina L.
  •   Davies, Mark (external author)
  •   Walker, Mark (external author)

Publication Date


  • 2020

Citation


  • Brouwer, S., Barnett, T., Ly, D., Kasper, K., De Oliveira, D., Rivera-Hernandez, T., Cork, A., McIntyre, L., Jespersen, M., Richter, J., Schulz, B., Dougan, G., Nizet, V., Yuen, K., You, Y., McCormick, J., Sanderson-Smith, M., Davies, M. & Walker, M. (2020). Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes. Nature Communications, 11 (1),

Scopus Eid


  • 2-s2.0-85091976357

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=2579&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/1551

Volume


  • 11

Issue


  • 1

Place Of Publication


  • United Kingdom