Drug development concerning metallo-β-lactamases in gram-negative bacteria.
Drug development concerning metallo-β-lactamases in gram-negative bacteria.
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DOI：
10.3389/fmicb.2022.959107
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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β-内酰胺自出现以来一直是临床关注的焦点，并且确实是对抗严重细菌感染的有力工具，但其有效性受到细菌耐药性的威胁，主要是丝氨酸和金属-β-内酰胺酶的产生。尽管金属-β-内酰胺酶曾经不太具有临床意义，但现在的威胁越来越大。金属-β-内酰胺酶介导的耐药性的快速传播对全世界的公共卫生构成了越来越大的挑战，并且包括大多数现有的抗菌化疗。遗憾的是，迄今为止，尚无临床可用的金属-β-内酰胺酶抑制剂。为了应对这一独特的挑战，研究人员正在探索对抗金属-β-内酰胺酶的多维策略。已经进行了几项研究来开发新的候选药物或校准现有的针对金属-β-内酰胺酶的药物。为了概述这一领域并激励更多研究人员进一步探索，我们概述了一些针对金属-β-内酰胺酶生产者的有前景的候选药物，重点关注大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌。本次综述中的候选药物包括新型抗菌药物、非抗菌药物、抗菌肽、天然产物和锌螯合剂，以及它们与现有抗生素的组合。本综述可为其他人探索候选金属-β-内酰胺酶提供思路和见解，并促进现有数据的改进以获得进一步令人信服的证据。
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.