title: SpyA, a C3-like ADP-ribosyltransferase, contributes to virulence in a mouse subcutaneous model of Streptococcus pyogenes infection.
abstract: Streptococcus pyogenes is an important human pathogen with an expansive repertoire of verified and putative virulence factors. Here we demonstrate that a mutant deficient in the production of the streptococcal ADP-ribosyltransferase SpyA generates lesions of reduced size in a subcutaneous mouse infection model. At early stages of infection, when the difference in lesion size is first established, inflamed tissue isolated from lesions of mice infected with spyA mutant bacteria has higher levels of mRNA encoding the chemokines CXCL1 and CCL2 than does tissue isolated from mice infected with wild-type bacteria. In addition, at these early times, the mRNA levels for the gene encoding the intermediate filament vimentin are higher in the mutant-infected tissue. As wound resolution progresses, mRNA levels of the gene encoding matrix metallopeptidase 2 are lower in mutant-infected tissue. Furthermore, we demonstrate that the spyA mutant is internalized more efficiently than wild-type bacteria by HeLa cells. We conclude that SpyA contributes to streptococcal pathogenesis in the mouse subcutaneous infection model. Our observations suggest that the presence of SpyA delays wound healing in this model.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Hoff
authors.forename: Mark
authors.initials: M
authors.lastname: DeWald
authors.forename: Steve L
authors.initials: SL
authors.lastname: Moseley
authors.forename: Carleen M
authors.initials: CM
authors.lastname: Collins
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000502:physiology; D054360:Chemokine CXCL1 / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D037521:Virulence Factors; D036002:ADP Ribose Transferases