%A Sakshi Agarwal %A Prabhakar Tiwari %A Amar Deep %A Saqib Kidwai %A Shamba Gupta %A Krishan Gopal Thakur %A Ramandeep Singh %O Copyright of this article belongs to OUP. %J The Journal of Infectious Diseases %T System wide analysis unravels differential regulation and in vivo essentiality of VapBC TA systems from Mycobacterium tuberculosis %X oxin-antitoxin (TA) systems are bicistronic genetic modules that are ubiquitously present in bacterial genomes. Mycobacterium tuberculosis (Mtb) genome encodes for 90 putative TA systems and these are considered to be associated with maintenance of bacterial genomic stability or its survival under unfavorable environment. Majority of these in Mtb have been annotated as belonging to the Virulence associated protein B and C (VapBC) family. However, their precise role in bacterial physiology has not been elucidated. Here, we functionally characterized VapC toxins from Mtb and show that overexpression of some homologs inhibits growth of M. bovis BCG in a bacteriostatic manner. Expression profiling of mRNA revealed that these VapC toxins were differentially induced upon exposure of Mtb to stress conditions. We also unraveled that transcriptional cross-activation exists between TA systems in Mtb. This study provides the first evidence for the essentiality of VapBC3 and VapBC4 systems in Mtb virulence. %D 2018 %R doi:10.1093/infdis/jiy109 %I OUP %L open2081