GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:22492855
| Citation |
Cameron, DR, Ward, DV, Kostoulias, X, Howden, BP, Moellering, RC Jr, Eliopoulos, GM and Peleg, AY (2012) Serine/threonine phosphatase Stp1 contributes to reduced susceptibility to vancomycin and virulence in Staphylococcus aureus. J. Infect. Dis. 205:1677-87 |
|---|---|
| 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. |
| Links |
PubMed PMC3415852 Online version:10.1093/infdis/jis252 |
| Keywords |
Animals; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Disease Models, Animal; Female; Gene Deletion; Gene Expression Profiling; Hemolysis; Histocytochemistry; Liver/pathology; Liver Abscess/microbiology; Liver Abscess/mortality; Liver Abscess/pathology; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism; Staphylococcal Infections/microbiology; Staphylococcal Infections/mortality; Staphylococcal Infections/pathology; Staphylococcus aureus/drug effects; Staphylococcus aureus/enzymology; Staphylococcus aureus/pathogenicity; Survival Analysis; Vancomycin Resistance; Virulence; Virulence Factors/genetics; Virulence Factors/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0016020: membrane |
ECO:0000315: |
C |
figure A. shows Vancomycin minimum inhibitory concentrations (MICs) were determined by Etest for A5937, A5937Δstp1, the complemented strain A5937Δstp1-C, and the vancomycin nonsusceptible isolate A5940. Values in parentheses represent MICs based on broth dilution.Figure B. shows Determination of vancomycin heteroresistance was performed using population analysis profiling. The stp1 deletion mutant had subpopulations that grew in the nonsusceptible range (>2 µg/mL); this was not seen in the parent strain (A5937) but was more pronounced in the clinical vancomycin-intermediate S. aureus daughter strain (A5940). CFU, colony-forming unit. Figure C. shows transmission electron microscopy was performed to determine cell wall thickness. Three representative cells from each strain are shown, and values represent mean cell wall thickness (95% confidence interval). |
complete | ||||
Notes
See also
References
See Help:References for how to manage references in GONUTS.
