DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection
- 15 July 2007
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 13 (8), 981-985
- https://doi.org/10.1038/nm1612
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 syndrome1. 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)2,3 and allowing the recruitment and activation of host plasminogen on the bacterial surface4. Here we describe how bacteriophage-encoded GAS DNase (Sda1), which facilitates the pathogen's escape from neutrophil extracellular traps5,6, 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.Keywords
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