ArticleNucleic acids research2013
The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV).
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 104 citations in OpenAlex.
- The stress response factor SigH mediates intrinsic resistance to multiple antibiotics inMicrobiology spectrum · 2026Article
- Cell-free genomics reveals fundamental regulatory principles of the Mycobacterium tuberculosis transcription cycle.Molecular cell · 2026Article
- Aromatic patch in whiB-like transcription factors facilitates primary sigma factor interaction in mycobacterium tuberculosis.Communications biology · 2026Article
- Exploring the Protein Landscape of Dormant Mycobacterium tuberculosis Through In Vitro Functional Studies.Advances in experimental medicine and biology · 2026Review
- 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
- Altered serine metabolism promotes drug tolerance inAntimicrobial agents and chemotherapy · 2024Article
- Beyond antibiotic resistance: The whiB7 transcription factor coordinates an adaptive response to alanine starvation in mycobacteria.Cell chemical biology · 2024Article
- Metabolic Rewiring ofMetabolites · 2024Review
- A virulence-associated small RNA MTS1338 activates an ABC transporter CydC for rifampicin efflux inFrontiers in microbiology · 2024Article
- Genomic Insights into the Pathogenicity and Drug-Resistance of aInfection and drug resistance · 2024Article
- Hierarchy and interconnected networks in the WhiB7 mediated transcriptional response to antibiotic stress in Mycobacterium abscessus.PLoS genetics · 2023Article
- Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.RSC medicinal chemistry · 2023Review
- Analysis of whiB7 in Mycobacterium tuberculosis reveals novel AT-hook deletion mutations.Scientific reports · 2023Article
- Beyond antibiotic resistance: thebioRxiv : the preprint server for biology · 2023Article
- Loss of allosteric regulation in α-isopropylmalate synthase identified as an antimicrobial resistance mechanism.npj antimicrobials and resistance · 2023Article
- Mycobacterium tuberculosis DprE1 Inhibitor OPC-167832 Is Active against Mycobacterium abscessusAntimicrobial agents and chemotherapy · 2022Article
- Distribution of Common and Rare Genetic Markers of Second-Line-Injectable-Drug Resistance in Mycobacterium tuberculosis Revealed by a Genome-Wide Association Study.Antimicrobial agents and chemotherapy · 2022Article
- CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis.Nature microbiology · 2022Article
- Genetic Determinants of Tigecycline Resistance inAntibiotics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis therapeutic options are limited by the high intrinsic antibiotic resistance of Mycobacterium tuberculosis. The putative transcriptional regulator WhiB7 is crucial for the activation of systems that provide resistance to diverse antibiotic classes. Here, we used in vitro run-off, two-hybrid assays, as well as mutagenic, complementation and protein pull-down experiments, to characterize WhiB7 as an auto-regulatory, redox-sensitive transcriptional activator in Mycobacterium smegmatis. We provide the first direct biochemical proof that a WhiB protein promotes transcription and also demonstrate that this activity is sensitive to oxidation (diamide). Its partner protein for transcriptional activation was identified as SigA, the primary sigma factor subunit of RNA polymerase. Residues required for the interaction mapped to region 4 of SigA (including R515H) or adjacent domains of WhiB7 (including E63D). WhiB7's ability to provide a specific spectrum of antibiotic-resistance was dependent on these residues as well as its C-terminal AT-hook module that binds to an AT-rich motif immediately upstream of the -35 hexamer recognized by SigA. These experimentally established constrains, combined with protein structure predictions, were used to generate a working model of the WhiB7-SigA-promoter complex. Inhibitors preventing WhiB7 interactions could allow the use of previously ineffective antibiotics for treatment of mycobacterial diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.