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DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection.
Walker, Mark J Hollands, Andrew Sanderson-Smith, Martina L Cole, Jason N Kirk, Joshua K Henningham, Anna McArthur, Jason D Dinkla, Katrin Aziz, Ramy K Kansal, Rita G
Walker, Mark J
Hollands, Andrew
Sanderson-Smith, Martina L
Cole, Jason N
Kirk, Joshua K
Henningham, Anna
McArthur, Jason D
Dinkla, Katrin
Aziz, Ramy K
Kansal, Rita G
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2007-08
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Abstract
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.
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DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. 2007, 13 (8):981-5 Nat. Med.
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en
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1078-8956