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Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through global genome mining

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  • Yong-Xin Li

    (Hong Kong University of Science and Technology
    Hong Kong University of Science and Technology)

  • Zheng Zhong

    (Hong Kong University of Science and Technology)

  • Wei-Peng Zhang

    (Hong Kong University of Science and Technology)

  • Pei-Yuan Qian

    (Hong Kong University of Science and Technology)

Abstract

The worldwide prevalence of infections caused by antibiotic-resistant Gram-negative bacteria poses a serious threat to public health due to the limited therapeutic alternatives. Cationic peptides represent a large family of antibiotics and have attracted interest due to their diverse chemical structures and potential for combating drug-resistant Gram-negative pathogens. Here, we analyze 7395 bacterial genomes to investigate their capacity for biosynthesis of cationic nonribosomal peptides with activity against Gram-negative bacteria. Applying this approach, we identify two novel compounds (brevicidine and laterocidine) showing bactericidal activities against antibiotic-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and colistin-resistant Escherichia coli, and an apparently low risk of resistance. The two peptides show efficacy against E. coli in a mouse thigh infection model. These findings may contribute to the discovery and development of Gram-negative antibiotics.

Suggested Citation

  • Yong-Xin Li & Zheng Zhong & Wei-Peng Zhang & Pei-Yuan Qian, 2018. "Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through global genome mining," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05781-6
    DOI: 10.1038/s41467-018-05781-6
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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. Kerry R. Buchholz & Mike Reichelt & Matthew C. Johnson & Sarah J. Robinson & Peter A. Smith & Steven T. Rutherford & John G. Quinn, 2024. "Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Christopher Jonkergouw & Ngong Kodiah Beyeh & Ekaterina Osmekhina & Katarzyna Leskinen & S. Maryamdokht Taimoory & Dmitrii Fedorov & Eduardo Anaya-Plaza & Mauri A. Kostiainen & John F. Trant & Robin H, 2023. "Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. 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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