Silva O N, Franco O L, Porto W F
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil; Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil.
Drugs Today (Barc). 2018 Dec;54(12):737-746. doi: 10.1358/dot.2018.54.12.2895652.
Bacterial resistance has become a problem of great concern all over the world. Gram-negative bacteria, including the Enterobacteriaceae family and Pseudomonas and Acinetobacter species, are among the leading causes of healthcare-associated infections. The rate of antibiotic resistance among these pathogens has increased dramatically in recent years, reaching a pandemic scale. The most common mechanism of resistance described for Gram-negative bacteria consists of beta-lactamase production. These enzymes hydrolyze beta-lactam antibiotics, which are among the most commonly used antimicrobial agents. As with other antibiotics, reports of bacterial resistance to these agents have increased in recent years. An alternative method for combating beta-lactamasemediated resistance has been the use of small beta-lactamase inhibitors (e.g., clavulanic acid and tazobactam), allowing the resurgence of beta-lactam antibiotics for the treatment of infections caused by beta-lactamase-producing bacteria. However, due to the beta-lactamase group's diversity, some of them present resistance to conventional beta-lactamase inhibitors. Bearing this in mind, in the last two decades, beta- lactamase inhibitor peptides have been developed as alternative adjuvants to strike back against such strains. In this review, we outline the most recent findings related to the design of beta-lactamase inhibitor peptides and their biotechnological potential.
细菌耐药性已成为全球备受关注的问题。革兰氏阴性菌，包括肠杆菌科、假单胞菌属和不动杆菌属，是医疗保健相关感染的主要原因之一。近年来，这些病原体中的抗生素耐药率急剧上升，已达到大流行程度。革兰氏阴性菌最常见的耐药机制是产生β-内酰胺酶。这些酶可水解β-内酰胺抗生素，而β-内酰胺抗生素是最常用的抗菌剂之一。与其他抗生素一样，近年来对这些药物产生细菌耐药性的报道也有所增加。对抗β-内酰胺酶介导的耐药性的一种替代方法是使用小的β-内酰胺酶抑制剂（如克拉维酸和他唑巴坦），从而使β-内酰胺抗生素能够重新用于治疗由产β-内酰胺酶细菌引起的感染。然而，由于β-内酰胺酶种类的多样性，其中一些对传统的β-内酰胺酶抑制剂具有耐药性。考虑到这一点，在过去二十年中，已开发出β-内酰胺酶抑制肽作为替代佐剂来对抗此类菌株。在本综述中，我们概述了与β-内酰胺酶抑制肽设计及其生物技术潜力相关的最新研究结果。
