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Efflux Pumps in Mycobacteria: Antimicrobial Resistance, Physiological Functions, and Role in Pathogenicity

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Efflux-Mediated Antimicrobial Resistance in Bacteria

Abstract

The emergence of multidrug and extensively drug-resistant tuberculosis represents a major threat to the control of the disease. Antimicrobial drug resistance in Mycobacterium tuberculosis is not merely a consequence of the occurrence of gene mutations in the drug targets but a balance between the acquisition of mutations and drug efflux. The low permeability of the mycobacterial cell wall acts synergistically with active drug efflux pumps, and this combined mechanism may particularly constitute the first step for the development of drug resistance. Besides drug efflux, efflux pumps also have physiological functions in the bacteria, and their expression is subjected to tight regulation in response to multiple environmental and physiological signals. Understanding the mechanisms underlying drug efflux, efflux pump regulation and their contribution for pathogenicity not only enables the development of more rapid and accurate tools for the guidance of antituberculosis therapy but also provides knowledge for the development of new therapeutic strategies.

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Acknowledgments

This work was partially supported by project PTDC/BIA-MIC/121859/2010 from Fundação para a Ciência e a Tecnologia (FCT, Portugal) and “Ciência sem Fronteiras/Professor Visitante Especial” (Proc.n° 88881.064961/2014-01) (Miguel Viveiros/IHMT/UNL recipient; Jose R. Lapa e Silva/UFRJ coordinator) by CAPES/MEC/Brazil. Diana Machado was supported by contract SFRH/BPD/100688/2014 from FCT, Portugal. Diana Machado, Isabel Couto and Miguel Viveiros thank the support to the Global Health and Tropical Medicine (GHTM) R & D Center through grant UID/Multi/04413/2013 from FCT.

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Authors and Affiliations

  1. Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil

    Pedro Eduardo Almeida da Silva, Daniela Ramos & Andrea Von Groll

  2. Unidade de Microbiologia Médica, Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal

    Diana Machado, Isabel Couto & Miguel Viveiros

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  1. Pedro Eduardo Almeida da Silva
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  2. Diana Machado
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  4. Isabel Couto
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  5. Andrea Von Groll
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  6. Miguel Viveiros
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Correspondence to Miguel Viveiros .

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  1. Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada

    Xian-Zhi Li

  2. U.S. Food and Drug Administration, Laurel, Maryland, USA

    Christopher A. Elkins

  3. University of Oklahoma, Norman, Oklahoma, USA

    Helen I. Zgurskaya

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da Silva, P.E.A., Machado, D., Ramos, D., Couto, I., Von Groll, A., Viveiros, M. (2016). Efflux Pumps in Mycobacteria: Antimicrobial Resistance, Physiological Functions, and Role in Pathogenicity. In: Li, XZ., Elkins, C., Zgurskaya, H. (eds) Efflux-Mediated Antimicrobial Resistance in Bacteria. Adis, Cham. https://doi.org/10.1007/978-3-319-39658-3_21

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