ArticleThe Journal of antimicrobial chemotherapy2019
Rifampicin and rifabutin resistance in 1003 Mycobacterium tuberculosis clinical isolates.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Article
- Strain diversity drives heterogeneous responses to tuberculosis combination therapy.Antimicrobial agents and chemotherapy · 2026Article
- Future-proofing tuberculosis therapy: framework for concurrent drug and resistance testing development.The Lancet. Infectious diseases · 2026Review
- Drug Resistance Patterns, Temporal Trends, and Risk Factors Among Elderly Tuberculosis Patients in Anhui, China: A Retrospective Study (2020-2024).Infection and drug resistance · 2026Article
- Strain diversity drives heterogeneous responses to tuberculosis combination therapy.bioRxiv : the preprint server for biology · 2025Article
- Reply to Schön et al., "Quality control and considering systematic MIC shifts are key when evaluating the role ofAntimicrobial agents and chemotherapy · 2025Article
- A comparative study of antibiotic resistance patterns in Mycobacterium tuberculosis.Scientific reports · 2025Article
- Drug-resistant tuberculosis: a persistent global health concern.Nature reviews. Microbiology · 2024Review
- Detection of multidrug-resistance in Mycobacterium tuberculosis by phenotype- and molecular-based assays.Annals of clinical microbiology and antimicrobials · 2024Article
- Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach.Nature communications · 2024Article
- Phenotype versus genotype discordant rifampicin susceptibility testing in tuberculosis: implications for a diagnostic accuracy.Microbiology spectrum · 2024Article
- Discordance Between Phenotypic and WGS-Based Drug Susceptibility Testing Results for Some Anti-Tuberculosis Drugs: A Snapshot Study of PairedInfection and drug resistance · 2024Article
- Clustering minimal inhibitory concentration data through Bayesian mixture models: An application to detectStatistical methods in medical research · 2023Article
- Quantitative measurement of antibiotic resistance inResearch square · 2023Article
- Analysis of Genome-Wide Mutational Dependence in Naturally Evolving Mycobacterium tuberculosis Populations.Molecular biology and evolution · 2023Article
- Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing ofThe European respiratory journal · 2022Article
- Differential Impact of theMicrobiology spectrum · 2022Article
- Mutually Exclusive Interactions of Rifabutin with Spatially Distinct Mycobacterial Cell Envelope Membrane Layers Offer Insights into Membrane-Centric Therapy of Infectious Diseases.ACS bio & med chem Au · 2022Article
- Tuberculosis Pathways to Care and Transmission of Multidrug Resistance in India.American journal of respiratory and critical care medicine · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesDrug-resistant TB remains a public health challenge. Rifamycins are among the most potent anti-TB drugs. They are known to target the RpoB subunit of RNA polymerase; however, our understanding of how rifamycin resistance is genetically encoded remains incomplete. Here we investigated rpoB genetic diversity and cross-resistance between the two rifamycin drugs rifampicin and rifabutin.
methodsWe performed WGS of 1003 Mycobacterium tuberculosis clinical isolates and determined MICs of both rifamycin agents on 7H10 agar using the indirect proportion method. We generated rpoB mutants in a laboratory strain and measured their antibiotic susceptibility using the alamarBlue reduction assay.
resultsOf the 1003 isolates, 766 were rifampicin resistant and 210 (27%) of these were rifabutin susceptible; 102/210 isolates had the rpoB mutation D435V (Escherichia coli D516V). Isolates with discordant resistance were 17.2 times more likely to harbour a D435V mutation than those resistant to both agents (OR 17.2, 95% CI 10.5-27.9, P value <10-40). Compared with WT, the D435V in vitro mutant had an increased IC50 of both rifamycins; however, in both cases to a lesser degree than the S450L (E. coli S531L) mutation.
conclusionsThe observation that the rpoB D435V mutation produces an increase in the IC50 of both drugs contrasts with findings from previous smaller studies that suggested that isolates with the D435V mutation remain rifabutin susceptible despite being rifampicin resistant. Our finding thus suggests that the recommended critical testing concentration for rifabutin should be revised.
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