VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response
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| Creator |
Agarwal, Sakshi
Sharma, Arun Bouzeyen, Rania Deep, Amar Sharma, Harsh Mangalaparthi, K Kiran Datta, Keshava K Kidwai, Saqib Gowda, Harsha Varadarajan, Raghavan Sharma, Datta Ravi Thakur, Krishan Gopal Singh, Ramandeep |
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| Subject |
QR Microbiology
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| Description |
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 ΔvapC22 mutant strain. Furthermore, both the ΔvapC22 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 ΔvapC22 mutant strain. Together, we demonstrate that the VapBC22 TA system belongs to a key regulatory network and is essential for M. tuberculosis pathogenesis
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| Publisher |
AAAS
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| Date |
2020-06-03
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| Type |
Article
PeerReviewed |
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| Relation |
https://advances.sciencemag.org/content/6/23/eaba6944
http://crdd.osdd.net/open/2580/ |
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| Identifier |
Agarwal, Sakshi and Sharma, Arun and Bouzeyen, Rania and Deep, Amar and Sharma, Harsh and Mangalaparthi, K Kiran and Datta, Keshava K and Kidwai, Saqib and Gowda, Harsha and Varadarajan, Raghavan and Sharma, Datta Ravi and Thakur, Krishan Gopal and Singh, Ramandeep (2020) VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response. Science Advances, 6 (23). pp. 1-14.
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