1. Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
- Author
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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, 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], and Walker, Mark J [0000-0001-7423-2769]
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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 - 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., 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.
- Published
- 2020
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