Singh Neelam, Chattopadhyay Gopinath, Sundaramoorthy Niranjana Sri, Varadarajan Raghavan, Singh Ramandeep
Centre for Tuberculosis Research, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, Faridabad-Gurugram expressway, Faridabad, Haryana, India.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India.
Commun Biol. 2025 Feb 27;8(1):327. doi: 10.1038/s42003-025-07663-2.
The VapBC toxin-antitoxin (TA) system, composed of VapC toxin and VapB antitoxin, has gained attention due to its relative abundance in members of the M. tuberculosis complex. Here, we have functionally characterised VapBC35 TA system from M. tuberculosis. We show that ectopic expression of VapC35 inhibits M. smegmatis growth in a bacteriostatic manner. Also, an increase in the VapB35 antitoxin to VapC35 toxin ratio results in a stronger binding affinity of the complex with the promoter-operator DNA. We show that VapBC35 is necessary for M. tuberculosis adaptation in oxidative stress conditions but is dispensable for M. tuberculosis growth in guinea pigs. Further, using a combination of co-expression studies and biophysical methods, we report that VapC35 also interacts with non-cognate antitoxin VapB3. Taken together, the present study advances our understanding of cross-interaction networks among VapBC TA systems from M. tuberculosis.
由VapC毒素和VapB抗毒素组成的VapBC毒素-抗毒素（TA）系统，因其在结核分枝杆菌复合群成员中相对丰富而受到关注。在此，我们对来自结核分枝杆菌的VapBC35 TA系统进行了功能表征。我们表明，VapC35的异位表达以抑菌方式抑制耻垢分枝杆菌的生长。此外，VapB35抗毒素与VapC35毒素的比例增加会导致该复合物与启动子-操纵子DNA的结合亲和力增强。我们表明，VapBC35对于结核分枝杆菌在氧化应激条件下的适应性是必需的，但对于结核分枝杆菌在豚鼠体内的生长是可有可无的。此外，通过共表达研究和生物物理方法相结合，我们报告VapC35还与非同源抗毒素VapB3相互作用。综上所述，本研究推进了我们对结核分枝杆菌VapBC TA系统之间交叉相互作用网络的理解。
