ArticleMolecular microbiology2012
Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 98 citations in OpenAlex.
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- Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment.PLoS biology · 2026Article
- Structural Basis of a Novel Heme Binding Bacterial One-Component Switch.bioRxiv : the preprint server for biology · 2026Article
- Aromatic patch in whiB-like transcription factors facilitates primary sigma factor interaction in mycobacterium tuberculosis.Communications biology · 2026Article
- Host- and pathogen-related determinants of pulmonaryEuropean respiratory review : an official journal of the European Respiratory Society · 2026Review
- Comparative genomics of the Streptomyces genus: insights into multi-stress-resistant genes for bioremediation.World journal of microbiology & biotechnology · 2025Article
- Increased proportion of growth-arrested bacilli in acidic pH adaptation promotesbioRxiv : the preprint server for biology · 2025Article
- Salinity-driven niche differentiation within the aquatic Luna-1 subcluster.ISME communications · 2025Article
- WhiB-like proteins: Diversity of structure, function and mechanism.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- MnoSR removal inFrontiers in cellular and infection microbiology · 2024Article
- Cysteine desulfurase (IscS)-mediated fine-tuning of bioenergetics and SUF expression preventsScience advances · 2023Article
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- Vanoxerine kills mycobacteria through membrane depolarization and efflux inhibition.Frontiers in microbiology · 2023Article
- A Hydrazine-Hydrazone Adamantine Compound Shows Antimycobacterial Activity and Is a Probable Inhibitor of MmpL3.Molecules (Basel, Switzerland) · 2022Article
- Moxifloxacin-Mediated Killing of Mycobacterium tuberculosis Involves Respiratory Downshift, Reductive Stress, and Accumulation of Reactive Oxygen Species.Antimicrobial agents and chemotherapy · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Host-generated oxidative stress is considered one of the main mechanisms constraining Mycobacterium tuberculosis (Mtb) growth. The redox-sensing mechanisms in Mtb are not completely understood. Here we show that WhiB4 responds to oxygen (O₂) and nitric oxide (NO) via its 4Fe-4S cluster and controls the oxidative stress response in Mtb. The WhiB4 mutant (MtbΔwhiB4) displayed an altered redox balance and a reduced membrane potential. Microarray analysis demonstrated that MtbΔwhiB4 overexpresses the antioxidant systems including alkyl hydroperoxidase (ahpC-ahpD) and rubredoxins (rubA-rubB). DNA binding assays showed that WhiB4 [4Fe-4S] cluster is dispensable for DNA binding. However, oxidation of the apo-WhiB4 Cys thiols induced disulphide-linked oligomerization, DNA binding and transcriptional repression, whereas reduction reversed the effect. Furthermore, WhiB4 binds DNA with a preference for GC-rich sequences. Expression analysis showed that oxidative stress repressed whiB4 and induced antioxidants in Mtb, while their hyper-induction was observed in MtbΔwhiB4. MtbΔwhiB4 showed increased resistance to oxidative stress in vitro and enhanced survival inside the macrophages. Lastly, MtbΔwhiB4 displayed hypervirulence in the lungs of guinea pigs, but showed a defect in dissemination to their spleen. These findings suggest that WhiB4 systematically calibrates the activation of oxidative stress response in Mtb to maintain redox balance, and to modulate virulence.
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