The broad‐spectrum antimicrobial peptide BMAP‐27B potentiates carbapenems against NDM‐producing pathogens in food animals

Abstract The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health. Carbapenem‐resistant Enterobacteriaceae (CRE), particularly those producing New Delhi Metallo‐β‐lactamase (NDM‐CRE), are prevalent in livestock and have acquired resistanc...

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Main Authors: Xiaoxiao Zhang, Yongdong Li, Lei Xu, Zhe Chen, Shengzhi Guo, Jun Liao, Min Ren, Yao Wang, Yi Chen, Chuanxing Wan, Jing Zhang, Xihui Shen
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:mLife
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Online Access:https://doi.org/10.1002/mlf2.70020
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Summary:Abstract The emergence and spread of antibiotic‐resistant pathogens in food animals pose a major threat to global public health. Carbapenem‐resistant Enterobacteriaceae (CRE), particularly those producing New Delhi Metallo‐β‐lactamase (NDM‐CRE), are prevalent in livestock and have acquired resistance to nearly all commonly used β‐lactam antibiotics. This study evaluated the efficacy of the antimicrobial peptide BMAP‐27B, a derivative of the cathelicidin family, against NDM‐CRE strains in food animals. BMAP‐27B showed potent antibacterial activity and rapid bactericidal effects against CRE, as well as comparable effects against human carbapenem‐resistant Acinetobacter baumannii. Furthermore, BMAP‐27B effectively penetrated and cleared biofilms formed by virulent strains of Escherichia coli and Klebsiella pneumoniae. Mechanistic studies indicated that BMAP‐27B exerts its antibacterial activity by disrupting bacterial membranes and inhibiting bacterial energy metabolism. BMAP‐27B effectively enhances the efficacy of carbapenems against NDM‐positive isolates by inhibiting efflux pump activity and chelating Zn2+ to inhibit NDM proteases, thus reversing carbapenem resistance in NDM‐CRE. Importantly, BMAP‐27B maintained excellent antimicrobial stability under extreme pH changes and high salt concentrations, along with resistance to serum and protease degradation. Investigations revealed that BMAP‐27B also shows ideal biocompatibility and therapeutic efficacy in vivo. In summary, the highly potent antibacterial activity of BMAP‐27B, along with its potential role as a broad‐spectrum antibiotic adjuvant, makes it a promising candidate for combating infections caused by foodborne NDM‐CRE and preventing pathogen transmission at the animal‐human‐environment interface.
ISSN:2770-100X