Letter abstract

Nature Medicine 13, 981 - 985 (2007)
Published online: 15 July 2007 | doi:10.1038/nm1612

DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection

Mark J Walker1, Andrew Hollands1, Martina L Sanderson-Smith1, Jason N Cole1, Joshua K Kirk1, Anna Henningham1, Jason D McArthur1, Katrin Dinkla2, Ramy K Aziz3,4, Rita G Kansal4,5, Amelia J Simpson6, John T Buchanan6, Gursharan S Chhatwal2, Malak Kotb4,5 & Victor Nizet6,7

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.

  1. School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
  2. Department of Microbial Pathogenesis and Vaccine Development, Helmholtz Centre for Infection Research, Braunschweig D-38124, Germany.
  3. Department of Microbiology and Immunology, Cairo University, Cairo, Egypt.
  4. The Veterans Affairs Medical Center, Memphis, Tennessee 38163, USA.
  5. The MidSouth Center for Biodefense and Security, Memphis, Tennessee 38163, USA.
  6. Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0687, USA.
  7. Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0687, USA.

Correspondence to: Mark J Walker1 e-mail: mwalker@uow.edu.au