DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection.
Most invasive bacterial infections are caused by species that more commonly colonize the human host with minimal symptoms. Although phenotypic or genetic correlates underlying a bacterium's shift to enhanced virulence have been studied, the in vivo selection pressures governing such shifts are poorly understood. The globally disseminated M1T1 clone of group A Streptococcus (GAS) is linked with the rare but life-threatening syndromes of necrotizing fasciitis and toxic shock syndrome. Mutations in the GAS control of virulence regulatory sensor kinase (covRS) operon are associated with severe invasive disease, abolishing expression of a broad-spectrum cysteine protease (SpeB) and allowing the recruitment and activation of host plasminogen on the bacterial surface. Here we describe how bacteriophage-encoded GAS DNase (Sda1), which facilitates the pathogen's escape from neutrophil extracellular traps, serves as a selective force for covRS mutation. The results provide a paradigm whereby natural selection exerted by the innate immune system generates hypervirulent bacterial variants with increased risk of systemic dissemination.
Walker
Mark J
MJ
School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
Hollands
Andrew
A
Sanderson-Smith
Martina L
ML
Cole
Jason N
JN
Kirk
Joshua K
JK
Henningham
Anna
A
McArthur
Jason D
JD
Dinkla
Katrin
K
Aziz
Ramy K
RK
Kansal
Rita G
RG
Simpson
Amelia J
AJ
Buchanan
John T
JT
Chhatwal
Gursharan S
GS
Kotb
Malak
M
Nizet
Victor
V
D000818:Animals; D002470:Cell Survival; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000382:microbiology; D010641:Phenotype; D012641:Selection, Genetic; D013290:Streptococcal Infections / Q000382:microbiology* / Q000473:pathology; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
D003850:Deoxyribonuclease I; C493845:Sda1 protein, Streptococcus pyogenes