Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
Autor: | Tania Rivera-Hernandez, Yuanhai You, Diane Ly, Johanna Richter, Gordon Dougan, Timothy C. Barnett, Amanda J. Cork, Mark J. Walker, Katherine J. Kasper, Mark R. Davies, Magnus G. Jespersen, Martina L. Sanderson-Smith, Victor Nizet, Liam McIntyre, Kwok Yung Yuen, David M. P. De Oliveira, John K. McCormick, Stephan Brouwer, Benjamin L. Schulz |
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Přispěvatelé: | Barnett, Timothy C. [0000-0002-3346-5117], De Oliveira, David M. P. [0000-0002-5085-7163], Jespersen, Magnus G. [0000-0001-9751-9877], Nizet, Victor [0000-0003-3847-0422], Yuen, Kwok-Yung [0000-0002-2083-1552], McCormick, John K. [0000-0003-3742-7289], Sanderson-Smith, Martina L. [0000-0002-6366-4993], Davies, Mark R. [0000-0001-6141-5179], Walker, Mark J. [0000-0001-7423-2769], Apollo - University of Cambridge Repository, Barnett, Timothy C [0000-0002-3346-5117], De Oliveira, David MP [0000-0002-5085-7163], Jespersen, Magnus G [0000-0001-9751-9877], McCormick, John K [0000-0003-3742-7289], Sanderson-Smith, Martina L [0000-0002-6366-4993], Davies, Mark R [0000-0001-6141-5179], Walker, Mark J [0000-0001-7423-2769] |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male 82/29 Erythrocytes 631/326/1320 Prophages General Physics and Astronomy medicine.disease_cause Group A 38/70 13/1 38/1 Superantigen 38/22 lcsh:Science Multidisciplinary Superantigens Streptococcus article Glutathione Streptolysins 38/77 Streptolysin 38/39 Female Infection Scarlet Fever Streptococcus pyogenes Science 030106 microbiology Virulence Exotoxins 13/106 Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Microbiology 38/91 Cell Line 82/80 03 medical and health sciences 14/34 Bacterial Proteins medicine Animals Humans 82/83 Prophage 692/420/254 Bacteriology General Chemistry 64/110 biochemical phenomena metabolism and nutrition medicine.disease Mice Inbred C57BL 030104 developmental biology 14/63 Mutation Scarlet fever bacteria Pharynx lcsh:Q |
Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-11 (2020) Nature Communications |
DOI: | 10.17863/cam.60387 |
Popis: | 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. The pathogenesis of Streptococcus pyogenes (GAS) causing scarlet fever has been associated with the presence of prophages, such as ΦHKU.vir, and their products. Here, the authors characterize the exotoxins SpeC and Spd1 of ΦHKU.vir and show these to act synergistically to facilitate nasopharyngeal colonization in mice. |
Databáze: | OpenAIRE |
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