Comparative proteomic analysis of vancomycin-sensitive and vancomycin-intermediate resistant S. aureus

Abstract

The extensive use of vancomycin has led to the development of MRSA ( methicillin- resistant Staphylococcus aureus ) strains with varying degrees of resistance to vancomycin. Accumulation of surplus cell wall material, decreased cross-linking of peptidoglycan, and/ or other cell wall alterations has been put forward to explain the VISA phenotype. To our knowledge, the protein profiles of hVISA and VISA strains are rarely analyzed via quantitative comparative proteomics. In this study, we subjected subcellular fractions isolated from two isogenic S. aureus strains ( vancomycin-intermediate resistant S. aureus ) to proteomic analysis, using an integrated quantitative proteomic approach assisted by bioinformatic analysis. In total,128 up-regulated proteins ( mainly AhpC, Adh, ArgF et al.) were identified,21 down-regulated proteins ( mainly LtaS, SdrD, MsrR, MsrB, OatA et al.) were obtained. The largest group of differentially expressed proteins is composed of enzymic proteins associated with metabolic and catalytic activity, which accounts for 50% and 51% of the total proteins, respectively.Some proteins which take an indispensable part in the regulatory networks of S. aureus with vancomycin treatment are related to Cell wall metabolism ( MurA ) , Cell adhesion ( SdrC, SdrD, ClfA , ClfB ) , Proteolysis ( Atl, LytM, SceD ) and Pressure response ( MsrA , MsrB, AhpC ) process.In conclusion, our proteomic study revealed regulatory proteins associated with vancomycin resistance in S. aureus, and some of these proteins are involved in the regulation of cell metabolism and function, providing protential targets for further development of drug resistance strategies.