VapBC22 toxin-antitoxin system from Mycobacterium tuberculosis is required for pathogenesis and modulation of host immune response.
Sakshi AgarwalArun SharmaRania BouzeyenAmar DeepHarsh SharmaKiran K MangalaparthiKeshava K DattaSaqib KidwaiHarsha GowdaRaghavan VaradarajanRavi Datta SharmaKrishan Gopal ThakurRamandeep SinghPublished in: Science advances (2020)
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.
Keyphrases
- mycobacterium tuberculosis
- escherichia coli
- immune response
- wild type
- pulmonary tuberculosis
- oxidative stress
- cell proliferation
- poor prognosis
- transcription factor
- pseudomonas aeruginosa
- biofilm formation
- staphylococcus aureus
- dendritic cells
- toll like receptor
- high fat diet induced
- dna damage
- signaling pathway
- type diabetes
- mass spectrometry
- single cell
- emergency department
- cystic fibrosis
- adipose tissue
- insulin resistance
- induced apoptosis
- hepatitis c virus
- heat shock
- ischemia reperfusion injury
- diabetic rats
- adverse drug
- antiretroviral therapy