Targeting mycobacterial efflux system to enhance tuberculosis therapy
Review article
Keywords:
drug resistance, efflux pump inhibitors, efflux Pump, MDR, mycobacterium tuberculosisAbstract
The worldwide health epidemic of tuberculosis (TB) persists. It still claims millions of lives each year despite medical breakthroughs. Long-term therapies, drug-resistant TB strains, and co-infections with conditions like HIV necessitate novel approaches. The use of Mycobacterium tuberculosis (Mtb) efflux pumps, which actively expel drugs and decrease their effectiveness, is one such approach. EPIs (Efflux Pump Inhibitors) have the potential to treat tuberculosis. This review offers insights into Mtb's immune evasion mechanisms, including its strong cell wall, granuloma formation, immunological modulation, and dormancy, as well as TB epidemiology, worldwide eradication efforts, and those processes. Dissecting Efflux Pumps highlights their significance in drug resistance, particularly against first-line TB medications. Efflux pumps are notorious for causing antibiotic resistance. EPIs may have benefits such as increased drug efficacy, resistance reversal, shortened treatment durations, less toxicity, improved adherence, and targeting of latent TB. The effectiveness of various EPI classes, including phenylalkylamines, protonophores, phenothiazines, and plant-derived derivatives, against Mtb growth and efflux pumps is evaluated. The creation of effective EPIs, a clearer understanding of efflux pump control, and essential clinical trials for validation remain obstacles.
Downloads
References
Zhang, Y. and W. Yew, Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015. The International Journal of Tuberculosis and Lung Disease, 2015. 19(11): p. 1276-1289.
Cruz-Knight, W. and L. Blake-Gumbs, Tuberculosis: an overview. Primary Care: Clinics in Office Practice, 2013. 40(3): p. 743-756.
Rodrigues, L., P. Cravo, and M. Viveiros, Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: a new strategy to revisit mycobacterial targets and repurpose old drugs. Expert review of anti-infective therapy, 2020. 18(8): p. 741-757.
Kumar, S.V., et al., A systematic review of different type of tuberculosis. Eur Rev Med Pharmacol Sci, 2010. 14(10): p. 831-43.
Almeida Da Silva, P.E. and J.C. Palomino, Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. Journal of antimicrobial chemotherapy, 2011. 66(7): p. 1417-1430.
Talbot, E.A. and B.J. Raffa, Mycobacterium tuberculosis, in Molecular Medical Microbiology. 2015, Elsevier. p. 1637-1653.
Grkovic, S., M.H. Brown, and R.A. Skurray. Transcriptional regulation of multidrug efflux pumps in bacteria. in Seminars in cell & developmental biology. 2001. Elsevier.
Webber, M. and L. Piddock, The importance of efflux pumps in bacterial antibiotic resistance. Journal of antimicrobial chemotherapy, 2003. 51(1): p. 9-11.
Kumar , S.V.e.a., A systematic review of different type of tuberculosis. Eur Rev Med Pharmacol Sci, 2010. 14(10): p. 831-43.
Barberis, I., et al., The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus. J Prev Med Hyg, 2017. 58(1): p. E9-e12.
Cruz Knight, B.G.e.a., Tuberculosis: an overview. Primary Care: Clinics in Office Practice, 2013. 40(3): p. 743-756.
Herzog, B., H, History of tuberculosis. Respiration, 1998. 65(1): p. 5-15.
Cattoir, V., Efflux-mediated antibiotics resistance in bacteria. Pathologie-biologie, 2004. 52(10): p. 607-616.
Alcalde-Rico, M.e.a., Multidrug efflux pumps at the crossroad between antibiotic resistance and bacterial virulence. Frontiers in microbiology, 2016. 7: p. 1483.
Balganesh, M.e.a., Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates. Antimicrobial agents and chemotherapy, 2012. 56(5): p. 2643-2651.
Balcewicz-Sablinska, M.K., et al., Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-α. The journal of Immunology, 1998. 161(5): p. 2636-2641.
Lubelski, J., W.N. Konings, and A.J. Driessen, Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. Microbiology and molecular biology reviews, 2007. 71(3): p. 463-476.
Sarathy, J.P., V. Dartois, and E.J.D. Lee, The role of transport mechanisms in Mycobacterium tuberculosis drug resistance and tolerance. Pharmaceuticals, 2012. 5(11): p. 1210-1235.
Poole, K., Efflux-mediated antimicrobial resistance. Journal of Antimicrobial Chemotherapy, 2005. 56(1): p. 20-51.
Li, X.-Z. and H. Nikaido, Efflux-mediated drug resistance in bacteria: an update. Drugs, 2009. 69: p. 1555-1623.
Balganesh, M., et al., Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates. Antimicrobial agents and chemotherapy, 2012. 56(5): p. 2643-2651.
da Silva, P.E.A., et al., Efflux as a mechanism for drug resistance in Mycobacterium tuberculosis. FEMS Immunology & Medical Microbiology, 2011. 63(1): p. 1-9.
Chang, G., Multidrug resistance ABC transporters. FEBS letters, 2003. 555(1): p. 102-105.
Laws, M., P. Jin, and K.M. Rahman, Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends in microbiology, 2022. 30(1): p. 57-68.
Yan, N., Structural advances for the major facilitator superfamily (MFS) transporters. Trends in biochemical sciences, 2013. 38(3): p. 151-159.
Kuroda, T. and T. Tsuchiya, Multidrug efflux transporters in the MATE family. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 2009. 1794(5): p. 763-768.
Nikaido, H., Structure and mechanism of RND-type multidrug efflux pumps. Advances in enzymology and related areas of molecular biology, 2011. 77: p. 1.
Jack, D.L., et al., A broad-specificity multidrug efflux pump requiring a pair of homologous SMR-type proteins. Journal of bacteriology, 2000. 182(8): p. 2311-2313.
Van Bambeke, F., E. Balzi, and P.M. Tulkens, Antibiotic efflux pumps. Biochemical pharmacology, 2000. 60(4): p. 457-470.
Alcalde-Rico, M., et al., Multidrug efflux pumps at the crossroad between antibiotic resistance and bacterial virulence. Frontiers in microbiology, 2016. 7: p. 1483.
Black, P.A., et al., Energy metabolism and drug efflux in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2014. 58(5): p. 2491-2503.
Lomovskaya, O. and W. Watkins, Inhibition of efflux pumps as a novel approach to combat drug resistance in bacteria. Journal of molecular microbiology and biotechnology, 2001. 3(2): p. 225-236.
Mc Dermott, P.F., R.D. Walker, and D.G. White, Antimicrobials: modes of action and mechanisms of resistance. International journal of toxicology, 2003. 22(2): p. 135-143.
Pule, C.M., et al., Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy. Journal of Antimicrobial Chemotherapy, 2016. 71(1): p. 17-26.
Braibant, M., P. Gilot, and J. Content, The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis. FEMS microbiology reviews, 2000. 24(4): p. 449-467.
Danilchanka, O., C. Mailaender, and M. Niederweis, Identification of a novel multidrug efflux pump of Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2008. 52(7): p. 2503-2511.
Gillespie, S.H., Evolution of drug resistance in Mycobacterium tuberculosis: clinical and molecular perspective. Antimicrobial agents and chemotherapy, 2002. 46(2): p. 267-274.
Rossi, E.D., J.A. Aínsa, and G. Riccardi, Role of mycobacterial efflux transporters in drug resistance: an unresolved question. FEMS microbiology reviews, 2006. 30(1): p. 36-52.
Zhang, Y., et al., Identification of novel efflux proteins Rv0191, Rv3756c, Rv3008, and Rv1667c involved in pyrazinamide resistance in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2017. 61(8): p. 10.1128/aac. 00940-17.
Pasca, M.R., et al., Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2004. 48(8): p. 3175-3178.
Choudhuri, B.S., et al., Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis. Biochemical Journal, 2002. 367(1): p. 279-285.
Silva, P.E., et al., Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2001. 45(3): p. 800-804.
Machado, D., et al., Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis. PloS one, 2012. 7(4): p. e34538.
Li, X.-Z., L. Zhang, and H. Nikaido, Efflux pump-mediated intrinsic drug resistance in Mycobacterium smegmatis. Antimicrobial agents and chemotherapy, 2004. 48(7): p. 2415-2423.
Gupta, A.K., et al., jefA (Rv2459), a drug efflux gene in Mycobacterium tuberculosis confers resistance to isoniazid & ethambutol. Indian Journal of Medical Research, 2010. 132(2): p. 176-188.
Pasca, M.R., et al., mmpL7 gene of Mycobacterium tuberculosis is responsible for isoniazid efflux in Mycobacterium smegmatis. Antimicrobial agents and chemotherapy, 2005. 49(11): p. 4775-4777.
Deoghare, S., Bedaquiline: a new drug approved for treatment of multidrug-resistant tuberculosis. Indian journal of pharmacology, 2013. 45(5): p. 536.
Te Brake, L.H., et al., The role of efflux pumps in tuberculosis treatment and their promise as a target in drug development: unraveling the black box. Annual review of pharmacology and toxicology, 2018. 58: p. 271-291.
Song, L. and X. Wu, Development of efflux pump inhibitors in antituberculosis therapy. International journal of antimicrobial agents, 2016. 47(6): p. 421-429.
Poole, K. and O. Lomovskaya, Can efflux inhibitors really counter resistance? Drug Discovery Today: Therapeutic Strategies, 2006. 3(2): p. 145-152.
Adams, K.N., J.D. Szumowski, and L. Ramakrishnan, Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. The Journal of infectious diseases, 2014. 210(3): p. 456-466.
Gupta, S., et al., Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor. American journal of respiratory and critical care medicine, 2013. 188(5): p. 600-607.
Andersen, C., I. Holland, and A. Jacq, Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E. coli. Biochimica et Biophysica Acta (BBA)-Biomembranes, 2006. 1758(10): p. 1587-1595.
Park, J.-W., et al., Effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP) on the dimerization of lipoprotein lipase. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism, 1997. 1344(2): p. 132-138.
Rodrigues, L., et al., Thioridazine and chlorpromazine inhibition of ethidium bromide efflux in Mycobacterium avium and Mycobacterium smegmatis. Journal of Antimicrobial Chemotherapy, 2008. 61(5): p. 1076-1082.
Ordway, D., et al., Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy, 2003. 47(3): p. 917-922.
Sharma, S., et al., Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis. Journal of Antimicrobial Chemotherapy, 2010. 65(8): p. 1694-1701.
Plummer, A.J., et al., Pharmacology of Rauwolfia alkaloids, including reserpine. Annals of the New York Academy of Sciences, 1954. 59(1): p. 8-21.
Ramón-García, S., et al., Role of the Mycobacterium tuberculosis P55 efflux pump in intrinsic drug resistance, oxidative stress responses, and growth. Antimicrobial agents and chemotherapy, 2009. 53(9): p. 3675-3682.
Daniele, R.P. and S.K. Holian, A potassium ionophore (valinomycin) inhibits lymphocyte proliferation by its effects on the cell membrane. Proceedings of the National Academy of Sciences, 1976. 73(10): p. 3599-3602.
Crowle, A.J., G.S. Douvas, and M.H. May, Chlorpromazine: a drug potentially useful for treating mycobacterial infections. Chemotherapy, 1992. 38(6): p. 410-419.
Amaral, L., et al., Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis. Journal of Antimicrobial Chemotherapy, 1996. 38(6): p. 1049-1053.
Jin, J., et al., The plant alkaloid piperine as a potential inhibitor of ethidium bromide efflux in Mycobacterium smegmatis. Journal of medical microbiology, 2011. 60(2): p. 223-229.
Suriyanarayanan, B. and R. Sarojini Santhosh, Docking analysis insights quercetin can be a non-antibiotic adjuvant by inhibiting Mmr drug efflux pump in Mycobacterium sp. and its homologue EmrE in Escherichia coli. Journal of Biomolecular Structure and Dynamics, 2015. 33(8): p. 1819-1834.
Zhang, Z., et al., Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates. BMC infectious diseases, 2015. 15(1): p. 1-7.
Kapp, E., et al., Small molecule efflux pump inhibitors in Mycobacterium tuberculosis: a rational drug design perspective. Mini reviews in medicinal chemistry, 2018. 18(1): p. 72-86.
Published
How to Cite
Issue
Section
Copyright (c) 2024 International journal of health sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Articles published in the International Journal of Health Sciences (IJHS) are available under Creative Commons Attribution Non-Commercial No Derivatives Licence (CC BY-NC-ND 4.0). Authors retain copyright in their work and grant IJHS right of first publication under CC BY-NC-ND 4.0. Users have the right to read, download, copy, distribute, print, search, or link to the full texts of articles in this journal, and to use them for any other lawful purpose.
Articles published in IJHS can be copied, communicated and shared in their published form for non-commercial purposes provided full attribution is given to the author and the journal. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
This copyright notice applies to articles published in IJHS volumes 4 onwards. Please read about the copyright notices for previous volumes under Journal History.
