Xiaoxiao Zhang, Yongdong Li, Lei Xu, Zhe Chen, Shengzhi Guo, Jun Liao, Min Ren, Yao Wang, Yi Chen, Chuanxing Wan, Jing Zhang, Xihui Shen
{"title":"广谱抗菌肽BMAP-27B增强碳青霉烯类抗食用动物中产生ndm的病原体。","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","doi":"10.1002/mlf2.70020","DOIUrl":null,"url":null,"abstract":"<p><p>The emergence and spread of antibiotic-resistant pathogens in food animals pose a major threat to global public health. Carbapenem-resistant <i>Enterobacteriaceae</i> (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 <i>Acinetobacter baumannii</i>. Furthermore, BMAP-27B effectively penetrated and cleared biofilms formed by virulent strains of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>. 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 Zn<sup>2+</sup> 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.</p>","PeriodicalId":94145,"journal":{"name":"mLife","volume":"4 3","pages":"275-293"},"PeriodicalIF":4.5000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207908/pdf/","citationCount":"0","resultStr":"{\"title\":\"The broad-spectrum antimicrobial peptide BMAP-27B potentiates carbapenems against NDM-producing pathogens in food animals.\",\"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\",\"doi\":\"10.1002/mlf2.70020\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The emergence and spread of antibiotic-resistant pathogens in food animals pose a major threat to global public health. Carbapenem-resistant <i>Enterobacteriaceae</i> (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 <i>Acinetobacter baumannii</i>. Furthermore, BMAP-27B effectively penetrated and cleared biofilms formed by virulent strains of <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>. 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 Zn<sup>2+</sup> 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.</p>\",\"PeriodicalId\":94145,\"journal\":{\"name\":\"mLife\",\"volume\":\"4 3\",\"pages\":\"275-293\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207908/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"mLife\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/mlf2.70020\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"mLife","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/mlf2.70020","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
The broad-spectrum antimicrobial peptide BMAP-27B potentiates carbapenems against NDM-producing pathogens in food animals.
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.