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

摘要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.

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