ArticleScientific reports2020
Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- The contribution of LepA to virulence and host cell invasion in Salmonella Typhimurium.BMC microbiology · 2026Article
- Article
- Ribosomal RNA methylation by GidB modulates discrimination of mischarged tRNA.bioRxiv : the preprint server for biology · 2026Article
- Reduced ROS-associated prophage induction in a lepA mutant contributes to increased fluoroquinolone persistence in Salmonella Typhimurium.Scientific reports · 2026Article
- The Conserved GTPase LepA May Contribute to the Final Proper Stabilization of the 3' Domain of the 30S Subunit During Ribosome Assembly.International journal of molecular sciences · 2026Article
- The identification Mycobacterium tuberculosis genes that modulate long term survival in the presence of rifampicin and streptomycin.Scientific reports · 2025Article
- Genomic Insight into Primary Adaptation ofAntibiotics (Basel, Switzerland) · 2025Article
- Article
- Genomic and Transcriptomic Analyses Reveal Multiple Strategies forFoods (Basel, Switzerland) · 2024Article
- The C-Terminal Acid Phosphatase Module of the RNase HI Enzyme RnhC Controls Rifampin Sensitivity and Light-Dependent Colony Pigmentation of Mycobacterium smegmatis.Journal of bacteriology · 2023Article
- Genomic and Transcriptomic Analysis Reveal Multiple Strategies for the Cadmium Tolerance inFoods (Basel, Switzerland) · 2022Article
- The evolving biology ofFrontiers in cellular and infection microbiology · 2022Review
- Rifamycin antibiotics and the mechanisms of their failure.The Journal of antibiotics · 2021Review
- Most-Probable-Number-Based Minimum Duration of Killing Assay for Determining the Spectrum of Rifampicin Susceptibility in Clinical Mycobacterium tuberculosis Isolates.Antimicrobial agents and chemotherapy · 2021Article
- Forward Genetics Reveals aFrontiers in microbiology · 2020Article
- Tuberculosis drug resistance profiling based on machine learning: A literature review.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesReview
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Although all wild-type bacterial populations exhibit antibiotic tolerance, bacterial mutants with higher or lower tolerant subpopulation sizes have been described. We recently showed that in mycobacteria, phenotypically-resistant subpopulations can grow in bulk-lethal concentrations of rifampicin, a first-line anti-tuberculous antibiotic targeting RNA polymerase. Phenotypic resistance was partly mediated by paradoxical upregulation of RNA polymerase in response to rifampicin. However, naturally occurring mutations that increase tolerance via this mechanism had not been previously described. Here, we used transposon insertional mutagenesis and deep sequencing (Tnseq) to investigate rifampicin-specific phenotypic resistance using two different in vitro models of rifampicin tolerance in Mycobacterium smegmatis. We identify multiple genetic factors that mediate susceptibility to rifampicin. Disruption of one gene, lepA, a translation-associated elongation factor, increased rifampicin tolerance in all experimental conditions. Deletion of lepA increased the subpopulation size that is able to grow in bulk-lethal rifampicin concentrations via upregulation of basal rpoB expression. Moreover, homologous mutations in lepA that are found in clinical Mycobacterium tuberculosis (Mtb) isolates phenocopy lepA deletion to varying degrees. Our study identifies multiple genetic factors associated with rifampicin tolerance in mycobacteria, and may allow correlation of genetic diversity of clinical Mtb isolates with clinically important phenotypes such as treatment regimen duration.
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