Dulanto Chiang Augusto, Dekker John P
Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.
Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA.
Commun Med (Lond). 2024 Aug 29;4(1):170. doi: 10.1038/s43856-024-00591-y.
The emergence and spread of bacteria resistant to commonly used antibiotics poses a critical threat to modern medical practice. Multiple classes of bacterial efflux pump systems play various roles in antibiotic resistance, and members of the resistance-nodulation-division (RND) transporter superfamily are among the most important determinants of efflux-mediated resistance in gram-negative bacteria. RND pumps demonstrate broad substrate specificities, facilitating extrusion of multiple chemical classes of antibiotics from the bacterial cell. Several newer beta-lactams and beta-lactam/beta-lactamase inhibitor combinations (BL/BLI) have been developed to treat infections caused by multidrug resistant bacteria. Here we review recent studies that suggest RND efflux pumps in clinically relevant gram-negative bacteria may play critical but underappreciated roles in the development of resistance to beta-lactams and novel BL/BLI combinations. Improved understanding of the genetic and structural basis of RND efflux pump-mediated resistance may identify new antibiotic targets as well as strategies to minimize the emergence of resistance.
对常用抗生素具有抗性的细菌的出现和传播对现代医学实践构成了重大威胁。多类细菌外排泵系统在抗生素抗性中发挥着不同作用，而抗性-结瘤-分裂（RND）转运蛋白超家族成员是革兰氏阴性菌中外排介导抗性的最重要决定因素之一。RND泵表现出广泛的底物特异性，有助于多种化学类别的抗生素从细菌细胞中排出。已经开发了几种新型β-内酰胺类药物以及β-内酰胺/β-内酰胺酶抑制剂组合（BL/BLI）来治疗由多重耐药菌引起的感染。在此，我们综述了近期的研究，这些研究表明临床相关革兰氏阴性菌中的RND外排泵可能在对β-内酰胺类药物和新型BL/BLI组合的抗性发展中发挥关键但未得到充分认识的作用。更好地理解RND外排泵介导抗性的遗传和结构基础可能会确定新的抗生素靶点以及尽量减少抗性出现的策略。
