Drug development concerning metallo-β-lactamases in gram-negative bacteria

Autor: Xiuyun Li, Jing Zhao, Bin Zhang, Xuexia Duan, Jin Jiao, Weiwei Wu, Yuxia Zhou, Hefeng Wang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Microbiology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2022.959107
Popis: β-Lactams have been a clinical focus since their emergence and indeed act as a powerful tool to combat severe bacterial infections, but their effectiveness is threatened by drug resistance in bacteria, primarily by the production of serine- and metallo-β-lactamases. Although once of less clinical relevance, metallo-β-lactamases are now increasingly threatening. The rapid dissemination of resistance mediated by metallo-β-lactamases poses an increasing challenge to public health worldwide and comprises most existing antibacterial chemotherapies. Regrettably, there have been no clinically available inhibitors of metallo-β-lactamases until now. To cope with this unique challenge, researchers are exploring multidimensional strategies to combat metallo-β-lactamases. Several studies have been conducted to develop new drug candidates or calibrate already available drugs against metallo-β-lactamases. To provide an overview of this field and inspire more researchers to explore it further, we outline some promising candidates targeting metallo-β-lactamase producers, with a focus on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Promising candidates in this review are composed of new antibacterial drugs, non-antibacterial drugs, antimicrobial peptides, natural products, and zinc chelators, as well as their combinations with existing antibiotics. This review may provide ideas and insight for others to explore candidate metallo-β-lactamases as well as promote the improvement of existing data to obtain further convincing evidence.
Databáze: Directory of Open Access Journals