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

Yong-Xin Li, Zheng Zhong, Wei-Peng Zhang and Pei-Yuan Qian ()
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Yong-Xin Li: 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

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05781-6

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