Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants

碳青霉烯酶活性的结构解析:理解现有抑制剂的作用机制并指导新型碳青霉烯佐剂的设计

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Abstract

Antimicrobial resistance challenges the effectiveness of carbapenem antibiotics as last-line therapy, due to the production of both serine and metallo-β-lactamase enzymes. β-Lactamase inhibitors currently available on the market include clavulanic acid, sulbactam, tazobactam, avibactam, relebactam and vaborbactam but, while they are active against serine β-lactamases, they are inactive against the zinc-containing metallo-β-lactamases. This review aims to discuss the distinctive structural qualities of β-lactamase enzymes and to summarise the efficacy of clinically approved and emerging β-lactamase inhibitors against clinically significant carbapenemases.

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