Elucidating the Roles of VraSR and GraSR, 2 Two-Component Regulatory Systems, Associated with Intermediate Vancomycin Resistance in Vancomycin-Intermediate Staphylococcus Aureus (VISA)
By Xin-Ee Tan (xinee2709@hotmail.com)
One of the biggest challenges in treating Staphylococcus aureus infections is that these bacteria are no longer inhibited by front line antibiotics. To make things worse, reduced susceptibility of S. aureus to vancomycin (the antibiotic of last resort for this bacterium) have been reported in the mid-1990s. Therefore, it is important to understand bacterial responses towards vancomycin to aid in identification of new drug targets. In this study, we examined the difference of protein expression (comparative proteomic profiling) between vancomycin susceptible and vancomycin resistant strains, and shortlisted a few proteins for further validation with biochemical assays. Through these, we found that S. aureus achieve intermediate vancomycin resistance by modifying cellular metabolism to increase cell wall thickness and to resist oxidative stresses. These metabolic alterations in turn imposed a genetic burden on S. aureus cells, causing them to down-regulate virulence to compensate for fitness cost. This study provided insight into the possible regulatory pathway associated with intermediate vancomycin resistance in S. aureus which is crucial for expanding the antibiotic pipeline against this bacterium.
