Parker Harley, Lorenc Rachel, Ruelas Castillo Jennie, Karakousis Petros C
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
Front Microbiol. 2020 Sep 30;11:573983. doi: 10.3389/fmicb.2020.573983. eCollection 2020.
complex (MAC) species are the most commonly isolated nontuberculous mycobacteria to cause pulmonary infections worldwide. The lengthy and complicated therapy required to cure lung disease due to MAC is at least in part due to the phenomenon of antibiotic tolerance. In this review, we will define antibiotic tolerance and contrast it with persistence and antibiotic resistance. We will discuss physiologically relevant stress conditions that induce altered metabolism and antibiotic tolerance in mycobacteria. Next, we will review general molecular mechanisms underlying bacterial antibiotic tolerance, particularly those described for MAC and related mycobacteria, including , with a focus on genes containing significant sequence homology in MAC. An improved understanding of antibiotic tolerance mechanisms can lay the foundation for novel approaches to target antibiotic-tolerant mycobacteria, with the goal of shortening the duration of curative treatment and improving survival in patients with MAC.
鸟分枝杆菌复合体(MAC)菌种是全球范围内最常分离出的引起肺部感染的非结核分枝杆菌。治愈MAC所致肺部疾病所需的漫长而复杂的治疗至少部分归因于抗生素耐受性现象。在本综述中,我们将定义抗生素耐受性,并将其与持续性和抗生素耐药性进行对比。我们将讨论诱导分枝杆菌代谢改变和抗生素耐受性的生理相关应激条件。接下来,我们将综述细菌抗生素耐受性的一般分子机制,特别是针对MAC和相关分枝杆菌所描述的机制,包括 ,重点关注MAC中具有显著序列同源性的基因。对抗生素耐受性机制的更好理解可为靶向抗生素耐受性分枝杆菌的新方法奠定基础,目标是缩短治愈性治疗的持续时间并提高MAC患者的生存率。