Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning, China.
Department of Rheumatology and Immunology, The Second Affiliated Hospital, University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Arch Microbiol. 2021 Dec 29;204(1):97. doi: 10.1007/s00203-021-02652-5.
Tuberculosis (TB) causes millions of deaths each year across the globe. Multiple drug-resistant (MDR) and extensively drug-resistant (XDR) mycobacterial strains have made the treatment extremely difficult. To overcome this hurdle, the development of new drug targets and an effective treatment strategy are desperately needed. This can be achieved by deciphering the role of essential genes and enzymes which are involved in cell survival. One such enzyme is glyoxalase II. The glyoxalase system (glyoxalase I and glyoxalase II) has a pivotal role in cellular survival and detoxification by converting methylglyoxal (MG) into lactate. Otherwise, the increased concentration of MG then modifies DNA, proteins, and lipids, resulting in abnormalities and cell death. Interestingly, the function and physiological role of glyoxalase II have remained undetermined in mycobacteria. In this study, the functional activity of MSMEG_2975 (putative glyoxalase II) after heterologous cloning and expression was determined. And the knockdown strain Mycobacterium smegmatis KD for MSMEG_2975 was constructed with tetracycline-inducible vector pMIND. The inducible knockdown of MSMEG_2975 affected bacterial growth, biofilm formation, transcriptome, and enhanced the susceptibility to antibiotics. This work represents mycobacterial glyoxalase II as a potential drug target against mycobacterial pathogens and indicates the crucial regulatory role of glyoxalase II in mycobacteria.
结核病（TB）每年在全球造成数百万人死亡。耐多药（MDR）和广泛耐药（XDR）分枝杆菌菌株使得治疗变得极其困难。为了克服这一障碍，迫切需要开发新的药物靶点和有效的治疗策略。这可以通过破译参与细胞存活的必需基因和酶的作用来实现。其中一种酶是甘油醛-3-磷酸脱氢酶 II。甘油醛-3-磷酸脱氢酶系统（甘油醛-3-磷酸脱氢酶 I 和甘油醛-3-磷酸脱氢酶 II）在细胞存活和解毒中起着关键作用，通过将甲基乙二醛（MG）转化为乳酸来实现。否则，MG 浓度的增加会修饰 DNA、蛋白质和脂质，导致异常和细胞死亡。有趣的是，甘油醛-3-磷酸脱氢酶 II 在分枝杆菌中的功能和生理作用仍未确定。在这项研究中，通过异源克隆和表达确定了 MSMEG_2975（假定的甘油醛-3-磷酸脱氢酶 II）的功能活性。并且使用四环素诱导型载体 pMIND 构建了 MSMEG_2975 的敲低菌株 Mycobacterium smegmatis KD。MSMEG_2975 的诱导敲低影响细菌生长、生物膜形成、转录组，并增强了对抗生素的敏感性。这项工作代表分枝杆菌甘油醛-3-磷酸脱氢酶 II 作为一种针对分枝杆菌病原体的潜在药物靶点，并表明甘油醛-3-磷酸脱氢酶 II 在分枝杆菌中具有关键的调节作用。
