title: Serine/threonine phosphatase Stp1 contributes to reduced susceptibility to vancomycin and virulence in Staphylococcus aureus.
abstract: The genetic mechanisms that contribute to reduced susceptibility to vancomycin in Staphylococcus aureus are complex and heterogeneous. In addition, debate is emerging as to the true effect of reduced susceptibility to vancomycin on staphylococcal virulence. To investigate this, comparative genomics was performed on a collection of vancomycin-exposed isogenic S. aureus pairs (14 strains in total). Previously described mutations were observed in genes such as vraG, agrA, yvqF, and rpoB; however, a new mechanism was identified involving a serine/threonine phosphatase, Stp1. After constructing an stp1 deletion mutant, we showed that stp1 is important in vancomycin susceptibility and cell wall biosynthesis. Gene expression studies showed that stp1 also regulates virulence genes, including a hemolysin, superantigen-like protein, and phenol-soluble modulin, and that the deletion mutant is attenuated in virulence in vivo. Stp1 provides a new link between vancomycin susceptibility and virulence in S. aureus.
authors.affiliation: Department of Microbiology,  Monash University, Melbourne,  Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Cameron
authors.forename: Doyle V
authors.initials: DV
authors.lastname: Ward
authors.forename: Xenia
authors.initials: X
authors.lastname: Kostoulias
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Howden
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006461:Hemolysis; D006651:Histocytochemistry; D008099:Liver / Q000473:pathology; D008100:Liver Abscess / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D016019:Survival Analysis; D020713:Vancomycin Resistance; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D010749:Phosphoprotein Phosphatases