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

Agarwal, S and Sharma, A and Bouzeyen, R and Deep, A and Sharma, H and Mangalaparthi, KK and Datta, KK and Kidwai, S and Gowda, H and Gowda, H and Varadarajan, R and Sharma, RD and Thakur, KG and Singh, R (2020) VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response. In: Science Advances, 6 (23).

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Abstract

Virulence-associated protein B and C toxin-antitoxin (TA) systems are widespread in prokaryotes, but their precise role in physiology is poorly understood. We have functionally characterized the VapBC22 TA system from Mycobacterium tuberculosis. Transcriptome analysis revealed that overexpression of VapC22 toxin in M. tuberculosis results in reduced levels of metabolic enzymes and increased levels of ribosomal proteins. Proteomics studies showed reduced expression of virulence-associated proteins and increased levels of cognate antitoxin, VapB22 in the �vapC22 mutant strain. Furthermore, both the �vapC22 mutant and VapB22 overexpression strains of M. tuberculosis were susceptible to killing upon exposure to oxidative stress and showed attenuated growth in Guinea pigs and mice. Host transcriptome analysis suggests upregulation of the transcripts involved in innate immune responses and tissue remodeling in mice infected with the �vapC22 mutant strain. Together, we demonstrate that the VapBC22 TA system belongs to a key regulatory network and is essential for M. tuberculosis pathogenesis. © 2020 The Authors.

Item Type:	Journal Article
Publication:	Science Advances
Publisher:	American Association for the Advancement of Science
Additional Information:	Copy right for this article belongs to American Association for the Advancement of Science
Keywords:	Mammals; Proteins; Proteomics; Toxic materials; Tubes (components), Host immune response; Innate immune response; Metabolic enzymes; Mycobacterium tuberculosis; Overexpression strain; Regulatory network; Ribosomal proteins; Transcriptome analysis, Immune system
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	08 Jan 2021 10:59
Last Modified:	08 Jan 2021 10:59
URI:	http://eprints.iisc.ac.in/id/eprint/65806

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