ArticlePloS one2025
Linking genetic and phenotypic bedaquiline resistance in Mycobacterium tuberculosis strains from Georgia.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
introductionResistance to bedaquiline - a novel, promising medication against tuberculosis (TB), is already emerging, and uncertainties regarding the role of the different resistance-conferring mutations complicate the development of molecular diagnostic tools for detecting resistance. Mutations in the three genes atpE, pepQ, and Rv0678 have been associated with increased minimum inhibitory concentrations (MICs) to bedaquiline in Mycobacterium tuberculosis (Mtb). Here, we studied the effect of known and novel mutations in these genes on the phenotypic susceptibility to bedaquiline in Mtb isolates from patients with drug-resistant TB in the country of Georgia.
methodsWe used retrospective Mtb isolates (2011-2019) with whole-genome sequencing data, and prospectively collected diagnostic isolates with phenotypic resistance (2019-2022) to bedaquiline at the Georgian National Reference Laboratory. We determined bedaquiline MIC values using the SensititreTM MYCOTB MIC plate. MIC of 0.12 μg/mL was defined as borderline and MIC ≥ 0.25 μg/mL as a resistant isolate. A phylogeny was inferred to assess the likely role of the identified variants in bedaquiline resistance, while taking into consideration population structure of the strains analyzed.
resultsWe analyzed a total of 69 Mtb isolates and identified 61 mutations across the three target genes. Seventeen (27.8%) of these variants were associated with borderline (0.12 μg/mL) or resistant (≥0.25 μg/mL) MICs to bedaquiline. In addition to six previously described bedaquiline resistance-conferring mutations in atpE and Rv0678, we identified two novel variants in Rv0678 (Leu95Ser and Ile108fs) likely involved in bedaquiline resistance. We found a Tyr92Cys mutation in Rv0678 in two epidemiologically linked isolates, which likely emerged as a consequence of previous exposure to clofazimine.
conclusionConsistent with previous reports, our study confirms that mutations in Rv0678 are the most frequent cause of bedaquiline resistance in Georgia, in addition to an increasing clinical relevance of mutations in atpE, while the role of pepQ mutations remains to be defined.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.