Evidence mapPaperPMID 40976821Full record

ArticleFolia microbiologica2025

Flurbiprofen restores rifampicin and isoniazid sensitivity in multidrug-resistant Mycobacterium tuberculosis putatively by inhibiting efflux pumps Rv0194 and Rv0933.

Padmasini Elango, Christy Rosaline Nirmal, Sam Ebenezer Rajadas, Rajkumar Ravi, Naresh Babu Chilamakuru, Azger Dusthackeer V N

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Article in Folia microbiologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Padmasini ElangoDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, No.1, Mayor Sathyamoorthy Salai, Chetpet, Chennai, 600031, India.
Christy Rosaline NirmalDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, No.1, Mayor Sathyamoorthy Salai, Chetpet, Chennai, 600031, India.
Sam Ebenezer RajadasDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, No.1, Mayor Sathyamoorthy Salai, Chetpet, Chennai, 600031, India.
Rajkumar RaviDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, No.1, Mayor Sathyamoorthy Salai, Chetpet, Chennai, 600031, India.
Naresh Babu ChilamakuruDepartment of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, K.R.Palli Cross, Anantapur, 515721, India.
Azger Dusthackeer V NDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, No.1, Mayor Sathyamoorthy Salai, Chetpet, Chennai, 600031, India. azgerdusthackeer.vn@icmr.gov.in.

Funding

National Institute for Research in Tuberculosis Fellowship/Bact/RA/Padmasini/31.10.2022National Institute for Research in Tuberculosis F.No. 3/1/3/PDF(21)/2019-HRD dt 18.03.2020National Institute for Research in Tuberculosis No. Fellowship/TB/40/2020-7030
6 · The paper itself

Abstract

asbtractMultidrug-resistant tuberculosis remains a global health challenge, necessitating novel therapeutic approaches. Efflux pumps, including Rv0194 and Rv0933, contribute to Mycobacterium tuberculosis resistance by actively extruding first-line drugs such as rifampicin and isoniazid. This study aimed to identify small-molecule inhibitors that target these pumps to restore drug susceptibility. Through in silico screening, six lead compounds were selected and evaluated for antimicrobial activity against ten MDR-TB clinical isolates. Among them, flurbiprofen and trichlorocarbinalide exhibited significant inhibitory effects, enhancing rifampicin and isoniazid activity in checkerboard synergy assays. These combinations reduced the minimum inhibitory concentrations of both drugs, confirming their potential to reverse resistance. Cytotoxicity assessments of peripheral blood mononuclear and THP-1 cells demonstrated favourable safety profiles. Mechanistic studies revealed increased expression of Rv0194 and Rv0933 upon rifampicin and isoniazid exposure, underscoring their role in drug resistance. Flurbiprofen and trichlorocarbinalide may enhance intracellular drug retention by inhibiting these efflux pumps, improving therapeutic efficacy. However, trichlorocarbinalide did not restore rifampicin or isoniazid sensitivity as efficiently as flurbiprofen did. These findings highlight flurbiprofen as a promising efflux pump inhibitor that could potentiate standard TB treatments and counteract resistance. Further studies using diverse clinical isolates and in vivo models are needed to validate its therapeutic potential.

Indexed as

Drug synergyEfflux pump inhibitorsFlurbiprofenMultidrug-resistant tuberculosisRv0194Rv0933

Identifiers

PMID40976821

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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 Socratic graph.