National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture and Rural Affairs, Beijing, 100193, China.
Nat Commun. 2022 Apr 7;13(1):1888. doi: 10.1038/s41467-022-29493-0.
The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, we show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics (such as lefamulin), which target the bacterial ribosome. The trade-off between vancomycin and pleuromutilins is mediated by epistasis between the van gene cluster and msrC, encoding an ABC-F protein that protects bacterial ribosomes from antibiotic targeting. In mouse models of vancomycin-resistant E. faecium colonization and septicemia, pleuromutilin treatment reduces colonization and improves survival more effectively than standard therapy (linezolid). Our findings suggest that pleuromutilins may be useful for the treatment of vancomycin-resistant E. faecium infections.
获得一种抗生素的耐药性有时会导致对第二种抗生素的交叉敏感性。在这里，我们表明，屎肠球菌对万古霉素的耐药性与对黏菌素类抗生素（如利奈唑胺）的敏感性显著增加有关，这些抗生素靶向细菌核糖体。万古霉素和黏菌素之间的权衡是由 van 基因簇和 msrC 之间的上位性介导的，msrC 编码一种 ABC-F 蛋白，可保护细菌核糖体免受抗生素靶向。在万古霉素耐药屎肠球菌定植和败血症的小鼠模型中，黏菌素类药物治疗比标准治疗（利奈唑胺）更有效地减少定植并提高存活率。我们的研究结果表明，黏菌素类药物可能对治疗万古霉素耐药屎肠球菌感染有用。
