ArticleAnnals of clinical microbiology and antimicrobials2024
The importance of heteroresistance and efflux pumps in bedaquiline-resistant Mycobacterium tuberculosis isolates from Iran.
Article in Annals of clinical microbiology and antimicrobials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Screening for heterogeneous drug resistance in tuberculosis and its impact on clinical prognosis: A comprehensive review.iScience · 2026Review
- Assessing the efficacy of combined treatment using bedaquiline against clinical isolates of multidrug-resistant Mycobacterium tuberculosis in vitro and the macrophage model.BMC microbiology · 2026Article
- Article
- Genetic surveillance of first- and second-line drug-resistant isolates of Mycobacterium tuberculosis in Peru.PloS one · 2026Article
- Investigation of delamanid, bedaquiline, and linezolid resistance rates and related gene mutations in multidrug-resistant Mycobacterium tuberculosis in regional tuberculosis reference laboratories of Iran.BMC microbiology · 2025Article
- Investigation of bedaquiline heteroresistance amongMicrobiology spectrum · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates.
methodsNineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP).
resultsAll 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ.
conclusionsOur results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates.
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