ArticleRedox biology2018
Multifaceted remodeling by vitamin C boosts sensitivity of Mycobacterium tuberculosis subpopulations to combination treatment by anti-tubercular drugs.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Insights into the host response to 'dormant' Mycobacterium tuberculosis utilizing 'Vitamin C-induced dormant Mtb' THP-1 cell infection model.BMC genomics · 2026Article
- NapR, a novel nucleoid-associated protein, regulates antioxidant defense in mycobacteria.mSphere · 2025Article
- Unveiling the properties of ascorbic acid against M. tb through in silico approach: A comparative drug-based study.Journal of molecular modeling · 2025Article
- Proteomic insights into mycobacterial responses to elevated riboflavin reveal a role for flavin-sequestering proteins in flavin homeostasis.Frontiers in tuberculosis · 2025Article
- Significance of Viable But Non-culturable (VBNC) State in Vibrios and Other Pathogenic Bacteria: Induction, Detection and the Role of Resuscitation Promoting Factors (Rpf).Current microbiology · 2024Review
- Molecular characteristics of drug-susceptible Mycobacterium tuberculosis clinical isolates based on treatment duration.Osong public health and research perspectives · 2024Article
- Breaking barriers: The potential of nanosystems in antituberculosis therapy.Bioactive materials · 2024Review
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- The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy.eLife · 2023Article
- A pro-oxidant property of vitamin C to overcome the burden of latentFrontiers in cellular and infection microbiology · 2023Review
- Types and functions of heterogeneity in mycobacteria.Nature reviews. Microbiology · 2022Review
- The Error-Prone Polymerase DnaE2 Mediates the Evolution of Antibiotic Resistance in Persister Mycobacterial Cells.Antimicrobial agents and chemotherapy · 2022Article
- Clinically encountered growth phenotypes of tuberculosis-causing bacilli and theirFrontiers in cellular and infection microbiology · 2022Review
- Tuberculosis: The success tale of less explored dormantFrontiers in cellular and infection microbiology · 2022Review
- Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review.Antibiotics (Basel, Switzerland) · 2021Review
- Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis.Scientific reports · 2021Article
- Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?Frontiers in immunology · 2021Review
- Theranostic Application of a Novel G-Quadruplex-Forming DNA Aptamer Targeting Malate Synthase of Mycobacterium tuberculosis.Molecular therapy. Nucleic acids · 2019Article
- Multiple transcription factors co-regulate the Mycobacterium tuberculosis adaptation response to vitamin C.BMC genomics · 2019Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Bacterial dormancy is a major impediment to the eradication of tuberculosis (TB), because currently used drugs primarily target actively replicating bacteria. Therefore, decoding of the critical survival pathways in dormant tubercle bacilli is a research priority to formulate new approaches for killing these bacteria. Employing a network-based gene expression analysis approach, we demonstrate that redox active vitamin C (vit C) triggers a multifaceted and robust adaptation response in Mycobacterium tuberculosis (Mtb) involving ~ 67% of the genome. Vit C-adapted bacteria display well-described features of dormancy, including growth stasis and progression to a viable but non-culturable (VBNC) state, loss of acid-fastness and reduction in length, dissipation of reductive stress through triglyceride (TAG) accumulation, protective response to oxidative stress, and tolerance to first line TB drugs. VBNC bacteria are reactivatable upon removal of vit C and they recover drug susceptibility properties. Vit C synergizes with pyrazinamide, a unique TB drug with sterilizing activity, to kill dormant and replicating bacteria, negating any tolerance to rifampicin and isoniazid in combination treatment in both in-vitro and intracellular infection models. Finally, the vit C multi-stress redox models described here also offer a unique opportunity for concurrent screening of compounds/combinations active against heterogeneous subpopulations of Mtb. These findings suggest a novel strategy of vit C adjunctive therapy by modulating bacterial physiology for enhanced efficacy of combination chemotherapy with existing drugs, and also possible synergies to guide new therapeutic combinations towards accelerating TB treatment.
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Registered trials
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