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A new antibiotic kills pathogens without detectable resistance

Author

Listed:
  • Losee L. Ling

    (NovoBiotic Pharmaceuticals)

  • Tanja Schneider

    (Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
    German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany)

  • Aaron J. Peoples

    (NovoBiotic Pharmaceuticals)

  • Amy L. Spoering

    (NovoBiotic Pharmaceuticals)

  • Ina Engels

    (Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
    German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany)

  • Brian P. Conlon

    (Antimicrobial Discovery Center, Northeastern University)

  • Anna Mueller

    (Institute of Medical Microbiology, Immunology and Parasitology—Pharmaceutical Microbiology Section, University of Bonn, Bonn 53115, Germany
    German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany)

  • Till F. Schäberle

    (German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, 53115 Bonn, Germany
    Institute for Pharmaceutical Biology, University of Bonn, Bonn 53115, Germany)

  • Dallas E. Hughes

    (NovoBiotic Pharmaceuticals)

  • Slava Epstein

    (Northeastern University)

  • Michael Jones

    (Selcia, Ongar, Essex CM5 0GS, UK)

  • Linos Lazarides

    (Selcia, Ongar, Essex CM5 0GS, UK)

  • Victoria A. Steadman

    (Selcia, Ongar, Essex CM5 0GS, UK)

  • Douglas R. Cohen

    (NovoBiotic Pharmaceuticals)

  • Cintia R. Felix

    (NovoBiotic Pharmaceuticals)

  • K. Ashley Fetterman

    (NovoBiotic Pharmaceuticals)

  • William P. Millett

    (NovoBiotic Pharmaceuticals)

  • Anthony G. Nitti

    (NovoBiotic Pharmaceuticals)

  • Ashley M. Zullo

    (NovoBiotic Pharmaceuticals)

  • Chao Chen

    (Antimicrobial Discovery Center, Northeastern University)

  • Kim Lewis

    (Antimicrobial Discovery Center, Northeastern University)

Abstract

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

Suggested Citation

  • Losee L. Ling & Tanja Schneider & Aaron J. Peoples & Amy L. Spoering & Ina Engels & Brian P. Conlon & Anna Mueller & Till F. Schäberle & Dallas E. Hughes & Slava Epstein & Michael Jones & Linos Lazari, 2015. "A new antibiotic kills pathogens without detectable resistance," Nature, Nature, vol. 517(7535), pages 455-459, January.
    • Handle: RePEc:nat:nature:v:517:y:2015:i:7535:d:10.1038_nature14098
    DOI: 10.1038/nature14098
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    Citations

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    Cited by:

    1. Zhuo Cheng & Bei-Bei He & Kangfan Lei & Ying Gao & Yuqi Shi & Zheng Zhong & Hongyan Liu & Runze Liu & Haili Zhang & Song Wu & Wenxuan Zhang & Xiaoyu Tang & Yong-Xin Li, 2024. "Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Nicole M. Revie & Kali R. Iyer & Michelle E. Maxson & Jiabao Zhang & Su Yan & Caroline M. Fernandes & Kirsten J. Meyer & Xuefei Chen & Iwona Skulska & Meea Fogal & Hiram Sanchez & Saif Hossain & Sheen, 2022. "Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Elizabeth M. Bach & Kelly S. Ramirez & Tandra D. Fraser & Diana H. Wall, 2020. "Soil Biodiversity Integrates Solutions for a Sustainable Future," Sustainability, MDPI, vol. 12(7), pages 1-20, March.
    4. Bin Ma & Caiyu Lu & Yiling Wang & Jingwen Yu & Kankan Zhao & Ran Xue & Hao Ren & Xiaofei Lv & Ronghui Pan & Jiabao Zhang & Yongguan Zhu & Jianming Xu, 2023. "A genomic catalogue of soil microbiomes boosts mining of biodiversity and genetic resources," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Kalinga Pavan T. Silva & Ganesh Sundar & Anupama Khare, 2023. "Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Christopher J. Barden & Fan Wu & J. Pedro Fernandez-Murray & Erhu Lu & Shengguo Sun & Marcia M. Taylor & Annette L. Rushton & Jason Williams & Mahtab Tavasoli & Autumn Meek & Alla Siva Reddy & Lisa M., 2024. "Computer-aided drug design to generate a unique antibiotic family," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    7. Josh L Espinoza & Chris L Dupont & Aubrie O’Rourke & Sinem Beyhan & Pavel Morales & Amy Spoering & Kirsten J Meyer & Agnes P Chan & Yongwook Choi & William C Nierman & Kim Lewis & Karen E Nelson, 2021. "Predicting antimicrobial mechanism-of-action from transcriptomes: A generalizable explainable artificial intelligence approach," PLOS Computational Biology, Public Library of Science, vol. 17(3), pages 1-25, March.
    8. Hiroshi Hamamoto & Suresh Panthee & Atmika Paudel & Kenichi Ishii & Jyunichiro Yasukawa & Jie Su & Atsushi Miyashita & Hiroaki Itoh & Kotaro Tokumoto & Masayuki Inoue & Kazuhisa Sekimizu, 2021. "Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    9. Xinghong Zhao & Xinyi Zhong & Shinong Yang & Jiarong Deng & Kai Deng & Zhengqun Huang & Yuanfeng Li & Zhongqiong Yin & Yong Liu & Jakob H. Viel & Hongping Wan, 2024. "Guiding antibiotics towards their target using bacteriophage proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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