VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response

• DOI: 10.1126/sciadv.aba6944
• Publication Date: 2020-06-03T23:15:28Z
• Authors: Sakshi Agarwal; Arun Sharma; Rania Bouzeyen; Amar Deep; Harsh Sharma; Kiran K. Mangalap...; Keshava K. Datta; Saqib Kidwai; Harsha Gowda; Raghavan Varadarajan; Ravi Datta Sharma; Krishan Gopal Thakur; Ramandeep Singh
• Keywords: Antitoxin; Pathogenesis; Host response

Virulence-associated protein B and C toxin-antitoxin (TA) systems are widespread in prokaryotes, but their precise role physiology is poorly understood. We have functionally characterized the VapBC22 TA system from Mycobacterium tuberculosis. Transcriptome analysis revealed that overexpression of VapC22 toxin M. tuberculosis results reduced levels metabolic enzymes increased ribosomal proteins. Proteomics studies showed expression virulence-associated proteins cognate antitoxin, VapB22 ΔvapC22 mutant strain. Furthermore, both strains were susceptible to killing upon exposure oxidative stress attenuated growth guinea pigs mice. Host transcriptome suggests upregulation transcripts involved innate immune responses tissue remodeling mice infected with Together, we demonstrate belongs a key regulatory network essential for pathogenesis.