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Home / Articles / Tuberculosis: Study describes new mutations in drug resistance

Tuberculosis: Study describes new mutations in drug resistance

January 29, 2018

Credits: iMed.ULisboa and INSA

A recent study, now published in the highly regarded scientific journal Nature Genetics, considerably expands  the present body of knowledge concerning the genetic determinants of drug resistance in M. tuberculosis. In this study, new genetic mutations associated with important second-line drugs for multidrug resistant tuberculosis treatment regimens such as cycloserine, ethionamide and para-amino salicylic acid are described. Also, the study identifies novel interactions between drug resistance associated genes that may contribute to increased resistance levels and, also highlights the role of efflux pumps (membrane proteins specialized in molecular transport) in the development of drug resistance across this bacterial species.

Beyond the more comprehensive and deeper knowledge on M. tuberculosis resistance mechanisms conveyed by this new data,  it will enable the inclusion of specific markers for drug resistance in new rapid molecular diagnosis tests, envisioning an increase in sensitivity and specificity, but foremost, enabling an early tuberculosis diagnosis that allows therapeutical adjustments in way that it becomes more effective against resistant bacilli, increasing the cure rates of multidrug and extensively drug resistant tuberculosis infected patients and therefore also halting its transmission and dissemination presently happening.

This new data assumes special relevance in the current context of the WHO’s initiative End TB Strategy, with a main goal of achieving TB elimination by 2035, that is supported, among other pillars, in an intensified research and innovation.

This study, to this date the most comprehensive and largest concerning the genetic basis of M. tuberculosis drug resistance, was led by the London School of Hygiene and Tropical Medicine and results from the analysis of whole genome sequencing data from 6 465 clinical isolates originating from over 35 contries, including Portugal. At the national level, the coordination was carried out by Miguel Viveiros, professor at Instituto de Higiene e Medicina Tropical and by Isabel Portugal and João Perdigão, teacher and researcher, respectively, at Instituto de Investigação do Medicamento of the Faculdade de Farmácia da Universidade de Lisboa, institutions which played a central role in drug resistant tuberculosis early diagnosis in Greater Lisbon between 2000 and 2012, with collaboration from the Instituto Nacional de Saúde Dr. Ricardo Jorge and Instituto Gulbenkian de Ciência.

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About GHTM

GHTM is a R&D Unit that brings together researchers 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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