Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes.
Animals
Bacterial Proteins
/ pharmacology
Cell Line
Erythrocytes
/ drug effects
Exotoxins
/ genetics
Female
Glutathione
/ metabolism
Humans
Male
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Pharynx
/ cytology
Prophages
/ genetics
Scarlet Fever
/ epidemiology
Streptococcus pyogenes
/ genetics
Streptolysins
/ pharmacology
Superantigens
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 10 2020
06 10 2020
Historique:
received:
21
12
2019
accepted:
01
09
2020
entrez:
7
10
2020
pubmed:
8
10
2020
medline:
30
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33024089
doi: 10.1038/s41467-020-18700-5
pii: 10.1038/s41467-020-18700-5
pmc: PMC7538557
doi:
Substances chimiques
Bacterial Proteins
0
Exotoxins
0
Streptolysins
0
Superantigens
0
streptolysin O
0
Glutathione
GAN16C9B8O
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5018Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
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