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。

IF 4.5 Q1 MICROBIOLOGY
mLife Pub Date : 2025-06-24 eCollection Date: 2025-06-01 DOI:10.1002/mlf2.70020
Xiaoxiao Zhang, Yongdong Li, Lei Xu, Zhe Chen, Shengzhi Guo, Jun Liao, Min Ren, Yao Wang, Yi Chen, Chuanxing Wan, Jing Zhang, Xihui Shen
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引用次数: 0

摘要

食用动物中耐抗生素病原体的出现和传播对全球公共卫生构成重大威胁。碳青霉烯耐药肠杆菌科(CRE),特别是那些产生新德里金属β-内酰胺酶(NDM-CRE)的肠杆菌科,普遍存在于牲畜中,并已对几乎所有常用的β-内酰胺类抗生素产生耐药性。本研究评价了抗菌肽BMAP-27B(抗菌肽家族的衍生物)对食用动物NDM-CRE菌株的抑制作用。BMAP-27B对CRE具有较强的抑菌活性和快速杀菌作用,对人耐碳青霉烯鲍曼不动杆菌也具有相当的抑菌效果。此外,BMAP-27B能有效穿透和清除大肠杆菌和肺炎克雷伯菌强毒菌株形成的生物膜。机制研究表明BMAP-27B通过破坏细菌膜和抑制细菌能量代谢来发挥抗菌活性。BMAP-27B通过抑制外排泵活性和螯合Zn2+抑制NDM蛋白酶,有效增强碳青霉烯类药物对NDM阳性分离株的药效,从而逆转NDM- cre对碳青霉烯类药物的耐药性。重要的是,BMAP-27B在极端pH变化和高盐浓度下保持了优异的抗菌稳定性,并具有抗血清和蛋白酶降解的能力。研究表明BMAP-27B在体内也表现出理想的生物相容性和治疗效果。综上所述,BMAP-27B的高效抗菌活性及其作为广谱抗生素佐剂的潜在作用,使其成为对抗食源性NDM-CRE感染和防止病原体在动物-人-环境界面传播的有希望的候选物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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