Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence
Drug resistance in Mycobacterium leprae is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in Mycobacterium tuberculosis, drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.03072/full |
| _version_ | 1828528249119965184 |
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| author | Diana Machado Diana Machado Emmanuel Lecorche Emmanuel Lecorche Emmanuel Lecorche Faiza Mougari Faiza Mougari Faiza Mougari Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Miguel Viveiros Miguel Viveiros |
| author_facet | Diana Machado Diana Machado Emmanuel Lecorche Emmanuel Lecorche Emmanuel Lecorche Faiza Mougari Faiza Mougari Faiza Mougari Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Miguel Viveiros Miguel Viveiros |
| author_sort | Diana Machado |
| collection | DOAJ |
| description | Drug resistance in Mycobacterium leprae is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in Mycobacterium tuberculosis, drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this perspective, we discuss known efflux pumps involved in M. tuberculosis drug resistance and virulence and investigate similar regions in the genome of M. leprae. In silico analysis reveals that the major M. tuberculosis efflux pumps known to be associated with drug resistance and virulence have been retained during the reductive evolutionary process that M. leprae underwent, e.g., RND superfamily, the ABC transporter BacA, and the MFS P55. However, some are absent (DinF, MATE) while others are derepressed (Mmr, SMR) in M. leprae reflecting the specific environment where M. leprae may live. The occurrence of several multidrug resistance efflux transporters shared between M. leprae and M. tuberculosis reveals potential implications in drug resistance and virulence. The conservation of the described efflux systems in M. leprae upon genome reduction indicates that these systems are potentially required for its intracellular survival and lifestyle. They potentially are involved in M. leprae drug resistance, which could hamper leprosy treatment success. Studying M. leprae efflux pumps as new drug targets is useful for future leprosy therapeutics, enhancing the global efforts to eradicate endemic leprosy, and prevent the emergence of drug resistance in afflicted countries. |
| first_indexed | 2024-12-11T21:49:50Z |
| format | Article |
| id | doaj.art-e51c34f739e540f8a4ed54f9a328bfa3 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-11T21:49:50Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-e51c34f739e540f8a4ed54f9a328bfa32022-12-22T00:49:30ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-12-01910.3389/fmicb.2018.03072414641Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and VirulenceDiana Machado0Diana Machado1Emmanuel Lecorche2Emmanuel Lecorche3Emmanuel Lecorche4Faiza Mougari5Faiza Mougari6Faiza Mougari7Emmanuelle Cambau8Emmanuelle Cambau9Emmanuelle Cambau10Emmanuelle Cambau11Miguel Viveiros12Miguel Viveiros13Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, PortugalStudy Group for Mycobacterial Infections (ESGMYC), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), Basel, SwitzerlandUniversité Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, FranceAPHP, Groupe Hospitalier Lariboisière Fernand-Widal, Laboratoire de Bacteriologie, Paris, FranceCentre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux, Paris, FranceUniversité Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, FranceAPHP, Groupe Hospitalier Lariboisière Fernand-Widal, Laboratoire de Bacteriologie, Paris, FranceCentre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux, Paris, FranceStudy Group for Mycobacterial Infections (ESGMYC), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), Basel, SwitzerlandUniversité Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, FranceAPHP, Groupe Hospitalier Lariboisière Fernand-Widal, Laboratoire de Bacteriologie, Paris, FranceCentre National de Référence des Mycobactéries et Résistance des Mycobactéries aux Antituberculeux, Paris, FranceGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, PortugalStudy Group for Mycobacterial Infections (ESGMYC), European Society for Clinical Microbiology and Infectious Diseases (ESCMID), Basel, SwitzerlandDrug resistance in Mycobacterium leprae is assumed to be due to genetic alterations in the drug targets and reduced cell wall permeability. However, as observed in Mycobacterium tuberculosis, drug resistance may also result from the overactivity of efflux systems, which is mostly unexplored. In this perspective, we discuss known efflux pumps involved in M. tuberculosis drug resistance and virulence and investigate similar regions in the genome of M. leprae. In silico analysis reveals that the major M. tuberculosis efflux pumps known to be associated with drug resistance and virulence have been retained during the reductive evolutionary process that M. leprae underwent, e.g., RND superfamily, the ABC transporter BacA, and the MFS P55. However, some are absent (DinF, MATE) while others are derepressed (Mmr, SMR) in M. leprae reflecting the specific environment where M. leprae may live. The occurrence of several multidrug resistance efflux transporters shared between M. leprae and M. tuberculosis reveals potential implications in drug resistance and virulence. The conservation of the described efflux systems in M. leprae upon genome reduction indicates that these systems are potentially required for its intracellular survival and lifestyle. They potentially are involved in M. leprae drug resistance, which could hamper leprosy treatment success. Studying M. leprae efflux pumps as new drug targets is useful for future leprosy therapeutics, enhancing the global efforts to eradicate endemic leprosy, and prevent the emergence of drug resistance in afflicted countries.https://www.frontiersin.org/article/10.3389/fmicb.2018.03072/fullantimicrobial resistanceefflux pumpsleprosymycobacteriatuberculosisvirulence |
| spellingShingle | Diana Machado Diana Machado Emmanuel Lecorche Emmanuel Lecorche Emmanuel Lecorche Faiza Mougari Faiza Mougari Faiza Mougari Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Emmanuelle Cambau Miguel Viveiros Miguel Viveiros Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence Frontiers in Microbiology antimicrobial resistance efflux pumps leprosy mycobacteria tuberculosis virulence |
| title | Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence |
| title_full | Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence |
| title_fullStr | Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence |
| title_full_unstemmed | Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence |
| title_short | Insights on Mycobacterium leprae Efflux Pumps and Their Implications in Drug Resistance and Virulence |
| title_sort | insights on mycobacterium leprae efflux pumps and their implications in drug resistance and virulence |
| topic | antimicrobial resistance efflux pumps leprosy mycobacteria tuberculosis virulence |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.03072/full |
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