title: Antituberculosis drugs: reducing efflux=increasing activity.
abstract: In mycobacteria, it was assumed that efflux pumps only had a marginal role in drug resistance. In recent years, owing to the need to find novel drugs against multidrug-resistant tuberculosis, it has become clear that efflux should not be ignored. Although efflux inhibitors have been very useful for characterizing in vitro the properties of efflux pumps, their usefulness in vivo is limited because of their toxicity. Alternatively, programs aimed at discovering novel drugs for treating tuberculosis should implement strategies to characterize efflux liability of candidate drugs. Here, we present an experimental approach for studying efflux of compounds selected under the More Medicines for Tuberculosis research project, and a few examples of how, for tuberculosis drug discovery, efflux matters.
authors.affiliation: Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina and BIFI, Universidad de Zaragoza, Zaragoza, Spain; CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain; Fundación Agencia Aragonesa para la Investigación y Desarrollo (ARAID), Zaragoza, Spain.
authors.forename: Liliana
authors.initials: L
authors.lastname: Rodrigues
authors.affiliation: TB Discovery Research, Infectious Disease Research Institute, Seattle, WA, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Parish
authors.affiliation: AstraZeneca India Private Limited, Hebbal, Bangalore, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Balganesh
authors.affiliation: Grupo de Genética de Micobacterias, Departamento de Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina and BIFI, Universidad de Zaragoza, Zaragoza, Spain; CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address: ainsa@unizar.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Ainsa
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins