Campodónico Victoria L, Rifat Dalin, Chuang Yu-Min, Ioerger Thomas R, Karakousis Petros C
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Computer Science and Engineering, Texas A&M University, College Station, TX, United States.
Front Microbiol. 2018 Mar 19;9:494. doi: 10.3389/fmicb.2018.00494. eCollection 2018.
(Mtb) mutations are associated with global metabolic remodeling. However, the net effects of mutations on Mtb physiology, metabolism and function are not completely understood. Based on previous work, we hypothesized that changes in the expression of cell wall molecules in Mtb mutant RpoB 526D lead to changes in cell wall permeability and to altered resistance to environmental stresses and drugs. The phenotypes of a fully drug-susceptible clinical strain of Mtb and its paired rifampin-monoresistant, RpoB H526D mutant progeny strain were compared. The mutant showed altered colony morphology, bacillary length and cell wall thickness, which were associated with increased cell wall permeability and susceptibility to the cell wall detergent sodium dodecyl sulfate (SDS) after exposure to nutrient starvation. Relative to the isogenic rifampin-susceptible strain, the RpoB H526D mutant showed altered bacterial cellular metabolic activity and an eightfold increase in susceptibility to the cell-wall acting drug vancomycin. Our data suggest that RpoB mutation H526D is associated with altered cell wall physiology and resistance to cell wall-related stress. These findings are expected to contribute to an improved understanding of the pathogenesis of drug-resistant infections.
结核分枝杆菌（Mtb）突变与整体代谢重塑相关。然而，突变对结核分枝杆菌生理学、代谢和功能的净效应尚未完全明了。基于先前的研究工作，我们推测结核分枝杆菌RpoB 526D突变体中细胞壁分子表达的变化会导致细胞壁通透性改变，并改变对环境应激和药物的抗性。比较了一株完全药敏的结核分枝杆菌临床菌株及其配对的耐利福平RpoB H526D突变子代菌株的表型。该突变体表现出菌落形态、杆菌长度和细胞壁厚度的改变，这些改变与营养饥饿后细胞壁通透性增加以及对细胞壁去污剂十二烷基硫酸钠（SDS）的敏感性增加有关。相对于同基因的利福平敏感菌株，RpoB H526D突变体表现出细菌细胞代谢活性改变，对作用于细胞壁的药物万古霉素的敏感性增加了八倍。我们的数据表明，RpoB H526D突变与细胞壁生理学改变以及对细胞壁相关应激的抗性有关。这些发现有望有助于增进对耐药感染发病机制的理解。
