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 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.

Keywords

antibacterial mechanism / antibiotic synergist / antimicrobial peptides / carbapenem resistance / NDMs

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