TY - JOUR
T1 - Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes
AU - Brouwer, Stephan
AU - Barnett, Timothy C.
AU - Ly, Diane
AU - Kasper, Katherine J.
AU - De Oliveira, David M.P.
AU - Rivera-Hernandez, Tania
AU - Cork, Amanda J.
AU - McIntyre, Liam
AU - Jespersen, Magnus G.
AU - Richter, Johanna
AU - Schulz, Benjamin L.
AU - Dougan, Gordon
AU - Nizet, Victor
AU - Yuen, Kwok Yung
AU - You, Yuanhai
AU - McCormick, John K.
AU - Sanderson-Smith, Martina L.
AU - Davies, Mark R.
AU - Walker, Mark J.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091976357&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18700-5
DO - 10.1038/s41467-020-18700-5
M3 - Article
C2 - 33024089
AN - SCOPUS:85091976357
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5018
ER -