Title |
DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection
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Published in |
Nature Medicine, July 2007
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DOI | 10.1038/nm1612 |
Pubmed ID | |
Authors |
Mark J Walker, Andrew Hollands, Martina L Sanderson-Smith, Jason N Cole, Joshua K Kirk, Anna Henningham, Jason D McArthur, Katrin Dinkla, Ramy K Aziz, Rita G Kansal, Amelia J Simpson, John T Buchanan, Gursharan S Chhatwal, Malak Kotb, Victor Nizet |
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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Geographical breakdown
Country | Count | As % |
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United States | 3 | 2% |
Germany | 1 | <1% |
Australia | 1 | <1% |
Netherlands | 1 | <1% |
Taiwan | 1 | <1% |
South Africa | 1 | <1% |
Unknown | 138 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 41 | 28% |
Researcher | 25 | 17% |
Student > Bachelor | 14 | 10% |
Student > Master | 14 | 10% |
Professor | 7 | 5% |
Other | 19 | 13% |
Unknown | 26 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 50 | 34% |
Immunology and Microbiology | 21 | 14% |
Biochemistry, Genetics and Molecular Biology | 17 | 12% |
Medicine and Dentistry | 15 | 10% |
Engineering | 3 | 2% |
Other | 11 | 8% |
Unknown | 29 | 20% |