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Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium

Author

Listed:
  • 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
    Ministry of Agriculture and Rural Affairs)

  • 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
    Ministry of Agriculture and Rural Affairs)

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.

Suggested Citation

  • 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 & Jian, 2022. "Collateral sensitivity to pleuromutilins in vancomycin-resistant Enterococcus faecium," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29493-0
    DOI: 10.1038/s41467-022-29493-0
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    References listed on IDEAS

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    1. Sohn G. Kim & Simone Becattini & Thomas U. Moody & Pavel V. Shliaha & Eric R. Littmann & Ruth Seok & Mergim Gjonbalaj & Vincent Eaton & Emily Fontana & Luigi Amoretti & Roberta Wright & Silvia Caballe, 2019. "Microbiota-derived lantibiotic restores resistance against vancomycin-resistant Enterococcus," Nature, Nature, vol. 572(7771), pages 665-669, August.
    2. Daniel Nichol & Joseph Rutter & Christopher Bryant & Andrea M. Hujer & Sai Lek & Mark D. Adams & Peter Jeavons & Alexander R. A. Anderson & Robert A. Bonomo & Jacob G. Scott, 2019. "Antibiotic collateral sensitivity is contingent on the repeatability of evolution," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Elizabeth J. Culp & Nicholas Waglechner & Wenliang Wang & Aline A. Fiebig-Comyn & Yen-Pang Hsu & Kalinka Koteva & David Sychantha & Brian K. Coombes & Michael S. Nieuwenhze & Yves V. Brun & Gerard D. , 2020. "Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling," Nature, Nature, vol. 578(7796), pages 582-587, February.
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    Cited by:

    1. Dennis Y. Liu & Laura Phillips & Darryl M. Wilson & Kelly M. Fulton & Susan M. Twine & Alex Wong & Roger G. Linington, 2023. "Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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