Provvedi Roberta, Boldrin Francesca, Falciani Francesco, Palù Giorgio, Manganelli Riccardo
Department of Biology, University of Padua, 35100 Padua, Italy.
Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35100 Padua, Italy.
Microbiology (Reading). 2009 Apr;155(Pt 4):1093-1102. doi: 10.1099/mic.0.024802-0.
In order to gain additional understanding of the physiological mechanisms used by bacteria to maintain surface homeostasis and to identify potential targets for new antibacterial drugs, we analysed the variation of the Mycobacterium tuberculosis transcriptional profile in response to inhibitory and subinhibitory concentrations of vancomycin. Our analysis identified 153 genes differentially regulated after exposing bacteria to a concentration of the drug ten times higher than the MIC, and 141 genes differentially expressed when bacteria were growing in a concentration of the drug eightfold lower than the MIC. Hierarchical clustering analysis indicated that the response to these different conditions is different, although with some overlap. This approach allowed us to identify several genes whose products could be involved in the protection from antibiotic stress targeting the envelope and help to confer the basal level of M. tuberculosis resistance to antibacterial drugs, such as Rv2623 (UspA-like), Rv0116c, PE20-PPE31, PspA and proteins related to toxin-antitoxin systems. Moreover, we also demonstrated that the alternative sigma factor sigma(E) confers basal resistance to vancomycin, once again underlining its importance in the physiology of the mycobacterial surface stress response.
为了进一步了解细菌维持表面稳态所使用的生理机制，并确定新型抗菌药物的潜在靶点，我们分析了结核分枝杆菌转录谱在抑制性和亚抑制性浓度万古霉素作用下的变化。我们的分析确定，将细菌暴露于比最低抑菌浓度（MIC）高10倍的药物浓度后，有153个基因受到差异调节；当细菌在比MIC低8倍的药物浓度中生长时，有141个基因差异表达。层次聚类分析表明，对这些不同条件的反应是不同的，尽管存在一些重叠。这种方法使我们能够鉴定出几个基因，其产物可能参与针对包膜的抗生素应激保护，并有助于赋予结核分枝杆菌对抗菌药物的基础抗性水平，如Rv2623（类UspA）、Rv0116c、PE20 - PPE31、PspA以及与毒素 - 抗毒素系统相关的蛋白质。此外，我们还证明了替代sigma因子sigma(E)赋予对万古霉素的基础抗性，再次强调了其在分枝杆菌表面应激反应生理学中的重要性。
