ArticleCell chemical biology2024
Beyond antibiotic resistance: The whiB7 transcription factor coordinates an adaptive response to alanine starvation in mycobacteria.
Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 16 citations in OpenAlex.
- Activation of the antibiotic resistance factor WhiB7 can stimulate aggregate biofilm formation in stationary phaseJournal of bacteriology · 2026Article
- Induced alanine auxotrophy as a therapeutic strategy against Mycobacterium tuberculosis.Research square · 2026Article
- Induced alanine auxotrophy as a therapeutic strategy againstbioRxiv : the preprint server for biology · 2026Article
- Genome scale CRISPRi reveals both shared and strain-specific vulnerabilities in genetically diverse drug-resistant strains of Mycobacterium tuberculosis.Nature communications · 2026Article
- Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.Nature microbiology · 2026Article
- Article
- Illuminating the mechanism: gene expression responses to antimicrobial photodynamic therapy.BMC genomics · 2026Review
- Article
- Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus.Nature microbiology · 2025Article
- Using host and bacterial genetic approaches to define virulence strategies and protective immunity duringmSphere · 2025Review
- AACS infectious diseases · 2025Article
- Multidrug tolerance conferred by loss-of-function mutations in anti-sigma factor RshA ofAntimicrobial agents and chemotherapy · 2024Article
- Tiny but mighty: Diverse functions of uORFs that regulate gene expression.Computational and structural biotechnology journal · 2024Review
- WhiB-like proteins: Diversity of structure, function and mechanism.Biochimica et biophysica acta. Molecular cell research · 2024Review
- CRISPRi functional genomics in bacteria and its application to medical and industrial research.Microbiology and molecular biology reviews : MMBR · 2024Review
- Identification of host factors for livestock and poultry viruses: genome-wide screening technology based on the CRISPR system.Frontiers in microbiology · 2024Review
- Hierarchy and interconnected networks in the WhiB7 mediated transcriptional response to antibiotic stress in Mycobacterium abscessus.PLoS genetics · 2023Article
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10 authors at 1 institution in 1 country.
Funding
Abstract
Pathogenic mycobacteria are a significant cause of morbidity and mortality worldwide. The conserved whiB7 stress response reduces the effectiveness of antibiotic therapy by activating several intrinsic antibiotic resistance mechanisms. Despite our comprehensive biochemical understanding of WhiB7, the complex set of signals that induce whiB7 expression remain less clear. We employed a reporter-based, genome-wide CRISPRi epistasis screen to identify a diverse set of 150 mycobacterial genes whose inhibition results in constitutive whiB7 expression. We show that whiB7 expression is determined by the amino acid composition of the 5' regulatory uORF, thereby allowing whiB7 to sense amino acid starvation. Although deprivation of many amino acids can induce whiB7, whiB7 specifically coordinates an adaptive response to alanine starvation by engaging in a feedback loop with the alanine biosynthetic enzyme, aspC. These findings describe a metabolic function for whiB7 and help explain its evolutionary conservation across mycobacterial species occupying diverse ecological niches.
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