Yang Wenjing, Chen Taoran, Zhou Qi, Xu Jiancheng
Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, China.
Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China.
J Antibiot (Tokyo). 2025 Jan;78(1):4-13. doi: 10.1038/s41429-024-00778-4. Epub 2024 Oct 17.
Linezolid binds to the 50S subunit of the bacterial ribosome, inhibiting bacterial protein synthesis by preventing the formation of the initiation complex. Oxazolidinone antimicrobial drugs represent the last line of defense in treating Staphylococcus aureus infections; thus, resistance to linezolid in S. aureus warrants high priority. This article examines the major mechanisms of resistance to linezolid in S. aureus, which include: mutations in the domain V of 23S rRNA (primarily G2576); chromosomal mutations in the rplC, rplD, and rplV genes (encoding the ribosomal uL3, uL4, and uL22 proteins, respectively); the exogenous acquisition of the methylase encoded by the chloramphenicol-florfenicol resistance (cfr) gene; the endogenous methylation or demethylation of 23S rRNA; the acquisition of optrA and poxtA resistance genes; and the existence of the LmrS multidrug efflux pump. In conclusion, these mechanisms mediate resistance through mutations or modifications to the bacterial target, thereby reducing the affinity of linezolid for the peptidyl transferase center (PTC) binding site or by preventing the binding of linezolid to the PTC through a ribosomal protective effect. The existence of additional, unexplained resistance mechanisms requires further investigation and verification.
利奈唑胺与细菌核糖体的50S亚基结合，通过阻止起始复合物的形成来抑制细菌蛋白质合成。恶唑烷酮类抗菌药物是治疗金黄色葡萄球菌感染的最后一道防线；因此，金黄色葡萄球菌对利奈唑胺的耐药性问题亟待高度关注。本文探讨了金黄色葡萄球菌对利奈唑胺耐药的主要机制，包括：23S rRNA结构域V中的突变（主要是G2576）；rplC、rplD和rplV基因（分别编码核糖体uL3、uL4和uL22蛋白）的染色体突变；由氯霉素-氟苯尼考耐药（cfr）基因编码的甲基化酶的外源获得；23S rRNA的内源性甲基化或去甲基化；optrA和poxtA耐药基因的获得；以及LmrS多药外排泵的存在。总之，这些机制通过对细菌靶点的突变或修饰介导耐药性，从而降低利奈唑胺对肽基转移酶中心（PTC）结合位点的亲和力，或通过核糖体保护作用阻止利奈唑胺与PTC结合。其他未解释的耐药机制的存在需要进一步研究和验证。
