Evidence map›Paper›PMID 40010155›Full record

ArticleEBioMedicine2025

Speeding up drug susceptibility testing in Mycobacterium tuberculosis using RNA biomarkers.

Amandine Sury, Margo Maex, Alain Baulard, Roby P Bhattacharyya, Stéphanie Depickère, Deborah T Hung, Paul Cos, Fadel Sayes, Wafa Frigui, Roland Brosch and 6 more

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Heteroresistance inFrontiers in cellular and infection microbiology · 2026
    Review
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

16 authors.

Amandine SuryScientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium; National Reference Centre of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium.
Margo MaexScientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium; National Reference Centre of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium.
Alain BaulardUniv. Lille, CNRS, Inserm, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, 59000, France; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UMS 2014 - PLBS, Lille, 59000, France.
Roby P BhattacharyyaThe Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA, 02142, USA; Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
Stéphanie DepickèrePlatform for Interventional Studies, Scientific Direction Infectious Diseases in Humans, Sciensano, Rue Juliette Wytsmanstraat 14, Brussels, 1050, Belgium.
Deborah T HungThe Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA, 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
Paul CosLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsbaan 212, Antwerp, 2610, Belgium.
Fadel SayesInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, 75015, France.
Wafa FriguiInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, 75015, France.
Roland BroschInstitut Pasteur, Université Paris Cité, CNRS UMR 6047, Unit for Integrated Mycobacterial Pathogenomics, Paris, 75015, France.
Vanessa MathysScientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium; National Reference Centre of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium.
Elizabeth M StreicherDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa.
Frederik De KeersmaekerDepartment of Epidemiology and Public Health, Sciensano, Juliette Wytsmanstraat 14, Brussel, 1050, Belgium.
Leen RigoutsMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, Antwerp, 2000, Belgium; Mycobacteria Culture Collection of the Belgian Belgian Coordinated Collections of Microorganisms, Nationalestraat 155, Antwerp, 2000, Belgium.
Pieter-Jan CeyssensScientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium; National Reference Centre of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium.
An Van den BosscheScientific Service Bacterial Diseases - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium; National Reference Centre of Mycobacteria and Tuberculosis - Infectious Diseases in Humans, Sciensano, Juliette Wytsmanstraat 14, Brussels, 1050, Belgium. Electronic address: An.VandenBossche@sciensano.be.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEfficient management of drug-resistant tuberculosis relies on fast diagnostics. To accelerate phenotypic drug susceptibility testing [pDST] for Mycobacterium tuberculosis [TB], we introduce TRACeR-TB, a test that infers drug resistance from antibiotic-specific mRNA biomarkers.

methodsTo develop TRACeR-TB, target genes were first identified through RNA sequencing experiments conducted on two drug-exposed, susceptible strains for four antitubercular drugs. Based on these findings, we designed drug-specific multiplex Quantigene panels to quantify mRNA levels of 8-9 biomarkers per drug (class), directly from crude cell lysates. The performance of TRACeR-TB was compared to the widely used Mycobacteria Growth Indicator Tube [MGIT] pDST by subjecting 238 strains with diverse drug resistance profiles to both methods, and aligning results to genotypic data. Furthermore, we explored TRACeR-TB's potential for evaluating molecules that enhance antibiotic efficacy, and investigated its applicability in macrophage models to assess Mtb's intracellular stress responses to drugs.

findingsAntituberculosis drugs trigger distinct transcriptional stress responses in susceptible, but not resistant bacilli, enabling a differentiation of the antibiotic phenotype in only 6 h. Validation on 238 strains showed TRACeR-TB had 100% (95% CI: 93·1-100%) sensitivity and 89·5% (95% CI: 74·7-97·2%) specificity compared to, respectively, 82·3% (95% CI: 69·2%-91·5%) and 94·8% (95% CI: 81·9%-99·4%) for MGIT pDST. TRACeR-TB specificity is likely underestimated due to the inclusion of isolates harbouring uncharacterised mutations. TRACeR-TB demonstrated 100% concordance with MGIT for drugs with reliable MGIT outcomes (moxifloxacin and isoniazid). Additionally, its sensitivity outperformed current rifampicin testing, detecting resistance in all borderline-resistant strains that MGIT missed, and bedaquiline testing. Furthermore, the assay detected the predicted effect of a novel drug booster and the intracellular drug-induced stress in macrophage models, highlighting its potential for drug optimisation.

interpretationTRACeR-TB is a complementary addition to current DSTs and can have a substantial impact on the TB diagnostics field. This tool can also play a vital role in identifying resistance mutations, thereby closing gaps in genotypic knowledge, and contribute to drug discovery and development.

fundingInstitut Pasteur, Agence Nationale de la Recherche.

Indexed as

Antitubercular AgentsMycobacterium tuberculosisRNA, BacterialBiomarkersDrug Resistance, BacterialHumansMacrophagesMicrobial Sensitivity TestsRNA, MessengerTuberculosisAntitubercular AgentsBiomarkersRNA, BacterialRNA, MessengerAntimicrobial resistanceBiomarkersDiagnosisRNATuberculosis

Identifiers

PMID40010155
PMCPMC11905850

What OpenQuestion holds

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LicenceCC BY-NC
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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.