ArticleThe Indian journal of medical research2011
Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates.
Article in The Indian journal of medical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
- Exploring allosteric efflux pump inhibitors and the role of bacterial membrane potential in modulating drug resistance.Frontiers in microbiology · 2026Review
- Impacts of MDR/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities.Current research in microbial sciences · 2024Review
- Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps.Antibiotics (Basel, Switzerland) · 2023Review
- Phenotypic heterogeneity in persisters: a novel 'hunker' theory of persistence.FEMS microbiology reviews · 2022Review
- The Orphan Response Regulator Rv3143 Modulates the Activity of the NADH Dehydrogenase Complex (Nuo) inFrontiers in cellular and infection microbiology · 2022Article
- In Vitro and In Silico Inhibition of Staphylococcus aureus Efflux Pump NorA by α-Pinene and Limonene.Current microbiology · 2021Article
- Multitarget Approaches against Multiresistant Superbugs.ACS infectious diseases · 2020Review
- Efflux pump inhibitors for bacterial pathogens: From bench to bedside.The Indian journal of medical research · 2019Review
- A novel mechanism of action of ketoconazole: inhibition of theInfection and drug resistance · 2019Article
- Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2018Article
- Molecular characteristics of ofloxacin mono-resistant Mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients.Journal of clinical laboratory analysis · 2018Article
- Drug detoxification dynamics explain the postantibiotic effect.Molecular systems biology · 2017Article
- Antibacterial Activity of Ciprofloxacin-Encapsulated Cockle Shells Calcium Carbonate (Aragonite) Nanoparticles and Its Biocompatability in Macrophage J774A.1.International journal of molecular sciences · 2016Article
- Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis.The Journal of antimicrobial chemotherapy · 2016Article
- Prevalence of mutations conferring resistance among multi- and extensively drug-resistant Mycobacterium tuberculosis isolates in China.The Journal of antibiotics · 2016Article
- Article
- New insights into TB physiology suggest untapped therapeutic opportunities.Immunological reviews · 2015Review
- The efflux pump inhibitor timcodar improves the potency of antimycobacterial agents.Antimicrobial agents and chemotherapy · 2015Article
- In vitro activity of rifampicin and verapamil combination in multidrug-resistant mycobacterium tuberculosis.PloS one · 2015Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
objectivesIn drug resistant, especially multi-drug resistant (MDR) tuberculosis, fluoroquinolones (FQs) are used as second line drugs. However, the incidence of FQ-resistant Mycobacterium tuberculosis is rapidly increasing which may be due to extensive use of FQs in the treatment of various other diseases. The most important known mechanism i.e., gyrA mutation in FQ resistance is not observed in a significant proportion of FQ resistant M. tuberculosis isolates suggesting that the resistance may be because of other mechanisms such as an active drug efflux pump. In this study we evaluated the role of the efflux pumps in quinolone resistance by using various inhibitors such as carbonyl cyanide m-chlorophenyl hydrazone (CCCP), 2,4-dinitrophenol (DNP) and verapamil, in clinical isolates of M. tuberculosis.
methodsA total of 55 M. tuberculosis clinical isolates [45 ofloxacin (OFL) resistant and 10 ofloxacin sensitive] were tested by Resazurin microtitre assay (REMA) to observe the changes in ofloxacin minimum inhibitory concentration (MIC) levels in presence of efflux inhibitors as compared to control (without efflux inhibitor).
resultsThe MIC levels of OFL showed 2-8 folds reduction in presence of CCCP (16/45; 35.5%), verapamil (24/45; 53.3%) and DNP (21/45; 46.6%) while in case of isolates identified as OFL sensitive these did not show any effect on ofloxacin MICs. In 11 of 45 (24.5%) isolates change in MIC levels was observed with all the three inhibitors. Overall 30 (66.6%) isolates had reduction in OFL MIC after treatment with these inhibitors. A total of eight isolates were sequenced for gyrA gene, of which, seven (87.5%) showed known mutations. Of the eight sequenced isolates, seven (87.5%) showed 2 to 8 fold change in MIC in presence of efflux inhibitors. INTERPRETATION &
conclusionsOur findings suggest the involvement of active efflux pumps of both Major Facilitator Super Family (MFS) family (inhibited by CCCP and DNP) and ATP Binding Cassette (ABC) transporters (inhibited by verapamil) in the development of OFL resistance in M. tuberculosis isolates. Epidemiological significance of these findings needs to be determined in prospective studies with appropriate number of samples/isolates.
Indexed as
Identifiers
21623040PMC3121286W1545358907What 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.