| Title | Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium |
| Authors | Li, Qian Chen, Shang Zhu, Kui Huang, Xiaoluo Huang, Yucheng Shen, Zhangqi Ding, Shuangyang Gu, Danxia Yang, Qiwen Sun, Hongli Hu, Fupin Wang, Hui Cai, Jiachang Ma, Bing Zhang, Rong Shen, Jianzhong |
| Affiliation | China Agr Univ, Coll Vet Med, Natl Ctr Vet Drug Safety Evaluat, Beijing 100193, Peoples R China Minist Agr & Rural Affairs, Lab Qual & Safety Risk Assessment Anim Prod Chem, Beijing Key Lab Detect Technol Anim Derived Food, Beijing 100193, Peoples R China Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Shenzhen 518055, Guangdong, Peoples R China Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Ctr Lab Med, Peoples Hosp, Hangzhou 310014, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Clin Lab, State Key Lab Complex Severe & Rare Dis, Beijing 100730, Peoples R China Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200040, Peoples R China Peking Univ, Dept Clin Lab, Peoples Hosp, Beijing 100044, Peoples R China Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Clin Lab, Hangzhou 310009, Peoples R China Henan Prov Peoples Hosp, Med Dept, Clin Lab, Zhengzhou 450003, Peoples R China |
| Keywords | ANTIBIOTIC-RESISTANCE EVOLUTION IDENTIFICATION GENE |
| Issue Date | 7-Apr-2022 |
| Publisher | NATURE COMMUNICATIONS |
| Abstract | The acquisition of resistance to one antibiotic sometimes leads to collateral sensitivity to a second antibiotic. Here, the authors show that vancomycin resistance in Enterococcus faecium is associated with a remarkable increase in susceptibility to pleuromutilin antibiotics, such as lefamulin. 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. |
| URI | http://hdl.handle.net/20.500.11897/642109 |
| DOI | 10.1038/s41467-022-29493-0 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
