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System wide analysis unravels differential regulation and in vivo essentiality of VapBC TA systems from Mycobacterium tuberculosis

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title System wide analysis unravels differential regulation and in vivo essentiality of VapBC TA systems from Mycobacterium tuberculosis
 
Creator Agarwal, Sakshi
Tiwari, Prabhakar
Deep, Amar
Kidwai, Saqib
Gupta, Shamba
Thakur, Krishan Gopal
Singh, Ramandeep
 
Subject QR Microbiology
 
Description 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.
 
Publisher OUP
 
Date 2018-05-05
 
Type Article
PeerReviewed
 
Relation http://dx.doi.org/10.1093/infdis/jiy109
http://crdd.osdd.net/open/2081/
 
Identifier Agarwal, Sakshi and Tiwari, Prabhakar and Deep, Amar and Kidwai, Saqib and Gupta, Shamba and Thakur, Krishan Gopal and Singh, Ramandeep (2018) System wide analysis unravels differential regulation and in vivo essentiality of VapBC TA systems from Mycobacterium tuberculosis. The Journal of Infectious Diseases. ISSN 0022-1899