Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium

Qian Li, Shang Chen, Kui Zhu (), Xiaoluo Huang, Yucheng Huang, Zhangqi Shen, Shuangyang Ding, Danxia Gu, Qiwen Yang, Hongli Sun, Fupin Hu, Hui Wang, Jiachang Cai, Bing Ma, Rong Zhang () and Jianzhong Shen ()
Additional contact information
Qian Li: College of Veterinary Medicine, China Agricultural University
Shang Chen: College of Veterinary Medicine, China Agricultural University
Kui Zhu: College of Veterinary Medicine, China Agricultural University
Xiaoluo Huang: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Yucheng Huang: College of Veterinary Medicine, China Agricultural University
Zhangqi Shen: College of Veterinary Medicine, China Agricultural University
Shuangyang Ding: Ministry of Agriculture and Rural Affairs
Danxia Gu: Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College
Qiwen Yang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Hongli Sun: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Fupin Hu: Huashan Hospital, Fudan University
Hui Wang: Peking University People’s Hospital
Jiachang Cai: Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang
Bing Ma: Henan Provincial People’s Hospital
Rong Zhang: Second Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang
Jianzhong Shen: College of Veterinary Medicine, China Agricultural University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29493-0

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