Work

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

Year: 2018

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-018-05781-6

Authors: Yong-Xin Li, Zheng Zhong, Wei-Peng Zhang, Pei-Yuan Qian

Institution: Hong Kong University of Science and Technology

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Applied Microbiology and Biotechnology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990