金黄色葡萄球菌对万古霉素耐药机制的研究进展OA

As an important gram-positive pathogen,Staphylococcus aureus has co-evolved its resistance to vancomycin through multiple mechanisms,which seriously threatens clinical anti-infective therapy.In this review,we systematically summarize the key pathways of drug resistance:cell wall thickening(increased peptidoglycan cross-linking due to activation of GraSR/WalKR signaling pathway),anti-biotic efflux(controversial role of NorA/MepA pump mediated drug efflux),ribosomal protection(erm gene-mediated rRNA methylation and ribosomal protein modification),biofilm formation(spatial barrier and metabolic inhibition of EPS matrix),and quorum sensing regu-lation(agr system multi-dimensional coordinated drug resistance network).Regulatory genes such as mgrA and vanA construct a three-dimensional defense system through epigenetic and metabolic reprogramming,while the resting state of retained bacteria further aggra-vates the difficulty of treatment.The clinical combination of vancomycin and β-lactam drugs can enhance the antibacterial effect,but the risk of nephrotoxicity and intestinal microbiota imbalance needs to be weighed.In the future,it is necessary to integrate multi-omics tech-nology to explore new drug resistance targets,develop TCS inhibitors and enzyme inhibitor adjuvants,and optimize the PK/PD model of combination therapy to meet the global challenges of drug-resistant bacterial infection.