2.50
Hdl Handle:
http://hdl.handle.net/10033/19833
Title:
DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection.
Authors:
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; Simpson, Amelia J; Buchanan, John T; Chhatwal, Gursharan S; Kotb, Malak; Nizet, Victor
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.
Affiliation:
School of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.
Citation:
DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. 2007, 13 (8):981-5 Nat. Med.
Journal:
Nature medicine
Issue Date:
Aug-2007
URI:
http://hdl.handle.net/10033/19833
DOI:
10.1038/nm1612
PubMed ID:
17632528
Type:
Article
Language:
en
ISSN:
1078-8956
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorWalker, Mark J-
dc.contributor.authorHollands, Andrew-
dc.contributor.authorSanderson-Smith, Martina L-
dc.contributor.authorCole, Jason N-
dc.contributor.authorKirk, Joshua K-
dc.contributor.authorHenningham, Anna-
dc.contributor.authorMcArthur, Jason D-
dc.contributor.authorDinkla, Katrin-
dc.contributor.authorAziz, Ramy K-
dc.contributor.authorKansal, Rita G-
dc.contributor.authorSimpson, Amelia J-
dc.contributor.authorBuchanan, John T-
dc.contributor.authorChhatwal, Gursharan S-
dc.contributor.authorKotb, Malak-
dc.contributor.authorNizet, Victor-
dc.date.accessioned2008-03-05T13:49:43Z-
dc.date.available2008-03-05T13:49:43Z-
dc.date.issued2007-08-
dc.identifier.citationDNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. 2007, 13 (8):981-5 Nat. Med.en
dc.identifier.issn1078-8956-
dc.identifier.pmid17632528-
dc.identifier.doi10.1038/nm1612-
dc.identifier.urihttp://hdl.handle.net/10033/19833-
dc.description.abstractMost 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.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCell Survivalen
dc.subject.meshDeoxyribonuclease Ien
dc.subject.meshHumansen
dc.subject.meshImmunity, Naturalen
dc.subject.meshMiceen
dc.subject.meshNeutrophilsen
dc.subject.meshPhenotypeen
dc.subject.meshSelection (Genetics)en
dc.subject.meshStreptococcal Infectionsen
dc.subject.meshStreptococcus pyogenesen
dc.subject.meshVirulenceen
dc.titleDNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection.en
dc.typeArticleen
dc.contributor.departmentSchool of Biological Sciences, University of Wollongong, Wollongong, New South Wales 2522, Australia.en
dc.identifier.journalNature medicineen
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