Evidence map›Paper›PMID 42832578›Full record

ArticlePloS one2026

Associating Mycobacterium tuberculosis genomic variants with minimum inhibitory concentrations to delamanid and pretomanid.

Ana Tsutsunava, Nestani Tukvadze, Zaza Avaliani, Galo A Goig, Levan Jugheli, Sebastien Gagneux, Russell R Kempker, Nino Maghradze

Abstract read
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ana TsutsunavaNational Center for Lung Health (NCLH), Tbilisi, Georgia.ORCID https://orcid.org/0000-0003-4111-6475
Nestani TukvadzeNational Center for Lung Health (NCLH), Tbilisi, Georgia.
Zaza AvalianiNational Center for Lung Health (NCLH), Tbilisi, Georgia.
Galo A GoigSwiss Tropical and Public Health Institute (Swiss TPH), Allschwil, Switzerland.
Levan JugheliSwiss Tropical and Public Health Institute (Swiss TPH), Allschwil, Switzerland.
Sebastien GagneuxSwiss Tropical and Public Health Institute (Swiss TPH), Allschwil, Switzerland.
Russell R KempkerDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.ORCID https://orcid.org/0000-0002-7188-4996
Nino MaghradzeNational Center for Lung Health (NCLH), Tbilisi, Georgia.ORCID https://orcid.org/0000-0003-1227-1900

Funding

Emory-Georgia TB Research Training ProgramD43TW007124 · FIC · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Nestani Tukvadze · 2004 to 2026
$4.6M
FIC NIH HHS D43 TW007124
6 · The paper itself

Abstract

Emerging resistance to delamanid (DLM) and pretomanid (Pa) threatens drug-resistant tuberculosis (DR-TB) treatment outcomes. The lack of rapid molecular diagnostics, due to limited knowledge of resistance-conferring mutations, along with standardization challenges for critical concentrations (CC) in phenotypic drug susceptibility testing (pDST) hinder resistance detection. Here, we explore the correlation between minimum inhibitory concentrations (MICs) and genomic variants of DLM and Pa resistance in Mycobacterium tuberculosis (Mtb). Seventeen Mtb isolates phenotypically resistant to DLM detected through routine pDST using the Mycobacterial Growth Indicator Tube (MGIT) system from 2021-2024 were selected from the National Reference Laboratory biobank in Tbilisi, Georgia. DLM/Pa MICs were determined using the Resazurin Microtiter Assay (REMA) with a DLM concentration range of 0.008-2 µg/ml, and a broader range of 0.125-32 µg/ml was utilized for Pa. To identify mutations associated with DLM/Pa resistance, isolates were subjected to whole genome sequencing (WGS). Of the seventeen Mtb isolates phenotypically resistant to DLM, eight (47%) manifested a MIC value below the DLM CC (0.06 µg/ml), with only one carrying a mutation in a gene associated with DLM/Pa resistance (fbiC). Among the remaining nine isolates with MICs above the CC, the premature stop codon mutation W88* in ddn gene predominated, present in five cases and associated with elevated DLM and Pa MICs (0.125-2 µg/ml and 2-8 µg/ml, respectively). Three isolates (19%) harbored novel, previously undescribed genetic variants, all within genes previously linked to resistance DLM/Pa (G35fs in ddn, Q317R and Q279H in fgd1, and C565W in fbiC). Our results support DLM and Pa resistance association with W88* and W678G mutations in ddn and fbiC genes respectively, currently graded as "uncertain significance" in the WHO catalogue of Mtb drug resistance-conferring mutations. Additionally, we observed previously undescribed mutations exclusively within genes linked to DLM/Pa susceptibility, prompting further investigation of their role in resistance.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisNitroimidazolesOxazolesDrug Resistance, BacterialGenome, BacterialHumansMicrobial Sensitivity TestsMutationAntitubercular AgentsNitroimidazolesOPC-67683Oxazolespretomanid

Identifiers

PMID42832578
PMCPMC13637882

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.