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
Předmět:
Zdroj: Frontiers in Microbiology; 9/15/2022, Vol. 13, p1-19, 19p
Abstrakt: 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-b-lactamases. Although once of less clinical relevance, metallo-β-lactamases are now increasingly threatening. The rapid dissemination of resistance mediated by metallo-b-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-b-lactamases. Several studies have been conducted to develop new drug candidates or calibrate already available drugs against metallo-b-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index