Metallo-β-Lactamases: A Major Threat to Human Health

• 作者: Christopher Selleck David L. Ollis Emer K. Phelan Gerhard Schenk Manfredi Miraula Nata?a Miti?
• 来源期刊: 美国分子生物学期刊(英文)
• 学科: 医学
• 关键词: Antibiotic Resistance Β-LACTAM ANTIBIOTICS Metallo-β-Lactamases Reaction Mechanism Metal Ion BINDING
• 年，卷（期）: 2014,（3）
• 页码范围: 89-104
• 页数: 16页
• 分类号: R73

摘要

Antibiotic resistance is one of the most significant challenges facing global healthcare. Since the 1940s, antibiotics have been used to fight infections, initially with penicillin and subsequently with various derivatives including cephalosporins, carbapenams and monobactams. A common characteristic of these antibiotics is the four-memberedβ-lactam ring. Alarmingly, in recent years an increasing number of bacteria have become resistant to these antibiotics. A major strategy employed by these pathogens is to use Zn(II)-dependent enzymes, the metallo-β-lactamases (MBLs), which hydrolyse theβ-lactam ring. Clinically useful MBL inhibitors are not yet available. Consequently, MBLs remain a major threat to human health. In this review biochemical properties of MBLs are discussed, focusing in particular on the interactions between the enzymes and the functionally essential metal ions. The precise role(s) of these metal ions is still debated and may differ between different MBLs. However, since they are required for catalysis, their binding site may present an alternative target for inhibitor design.