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

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 […]
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In vitro and in silico analysis of the efficiency of tetrahydropyridines as drug efflux inhibitors in Escherichia coli

The objectives of this study were to evaluate tetrahydropyridine derivatives as efflux inhibitors and to understand the mechanism of action of the compounds by in silico studies. Minimum inhibitory concentration (MIC) determination, fluorometric methods and docking simulations were performed. The compounds NUNL02, NUNL09 and NUNL10 inhibited efflux, and NUNL02 is very likely a substrate of […]
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Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates of Mycobacterium tuberculosis

Numerous studies show efflux as a universal bacterial mechanism contributing to antibiotic resistance and also that the activity of the antibiotics subject to efflux can be enhanced by the combined use of efflux inhibitors. Nevertheless, the contribution of efflux to the overall drug resistance levels of clinical isolates of Mycobacterium tuberculosis is poorly understood and […]
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Activity of rifabutin and hemi-synthetic derivatives against Mycobacterium abscessus

BACKGROUND: Mycobacterium abscessus causes a wide range of clinical diseases that are difficult to treat. This microorganism is resistant not only to the classical antituberculosis agents but also to most of the antimicrobials that are currently available, resulting in limited therapeutic options and treatment failure. This scenario stresses the need to search for new drugs […]
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Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations […]
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GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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