β-Lactamase inhibitor peptides as the new strategies to overcome bacterial resistance.

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.