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
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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