Parameters governing invasive disease propensity of non-M1 serotype group A streptococci.
Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propensity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. M1T1 GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections.
Maamary
Peter G
PG
School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia.
Sanderson-Smith
Martina L
ML
Aziz
Ramy K
RK
Hollands
Andrew
A
Cole
Jason N
JN
McKay
Fiona C
FC
McArthur
Jason D
JD
Kirk
Joshua K
JK
Cork
Amanda J
AJ
Keefe
Rachael J
RJ
Kansal
Rita G
RG
Sun
Hongmin
H
Taylor
William L
WL
Chhatwal
Gursharan S
GS
Ginsburg
David
D
Nizet
Victor
V
Kotb
Malak
M
Walker
Mark J
MJ
D000818:Animals; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000032:analysis*; D018450:Disease Progression; D005816:Genetic Complementation Test; D000071677:Histidine Kinase; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D013297:Streptococcus pyogenes / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence / Q000235:genetics
D004269:DNA, Bacterial; D047908:Intracellular Signaling Peptides and Proteins; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase
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