Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
BMC Microbiol. 2020 May 25;20(1):132. doi: 10.1186/s12866-020-01802-x.
Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance.
The effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p < 0.05 and p < 0.01) was shown.
LipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.
由于耐药性的发展，结核病（TB）的死亡率有所增加，但其机制尚未完全阐明。我们的研究小组在耐药结核分枝杆菌临床分离株中发现 lipF 基因表达水平降低。本研究旨在评估脂酶 F（LipF）表达对分枝杆菌药物耐药性的影响。
通过使用 Resazurin 微量滴定板和生长动力学来确定分枝杆菌中 lipF 的表达对抗结核药物耐药性的影响。异位 LipF 的功能得到了证实。LipF 的表达将利福平（RIF）和链霉素（STR）的最小抑菌浓度（MIC）分别从 3.12μg/mL 降低到 1.6μg/mL 和 0.25μg/mL，与无 LipF 表达的对照菌株相比，RIF 和 STR 存在时分枝杆菌的生长明显受到抑制（p<0.05 和 p<0.01）。
LipF 的表达与分枝杆菌中 RIF 和 STR 敏感性的增加有关。LipF 表达减少可能导致分枝杆菌对 RIF 和 STR 的耐药性发展。我们的研究结果为理解分枝杆菌药物耐药机制提供了相关信息。
