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Genomics and the chemotherapy of leprosy

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Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

John McKinney, Neeraj Dhar, Zela Alexandria-Mae Martin

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Cambridge2023

Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania

Jacques Fellay, Zhi Ming Xu

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC populat ...

PUBLIC LIBRARY SCIENCE2023

In-Cell Quantification of Drugs by Magic-Angle Spinning Dynamic Nuclear Polarization NMR

David Lyndon Emsley, Pierrick Berruyer, Andrea Bertarello

The determination of intracellular drug concentrations can provide a better understanding of the drug function and efficacy. Ideally, this should be performed nondestructively, with no modification of either the drug or the target, and with the capability ...

AMER CHEMICAL SOC2022

A new paradigm for leprosy diagnosis based on host gene expression

Stewart Cole, Andrej Benjak, Charlotte Avanzi, Philippe Busso, Thyago Leal Calvo

Author summary Despite effective treatment, leprosy is still a significant public health issue in more than 120 countries, with more than 200 000 new cases yearly. The disease is caused mainly by Mycobacterium leprae, a slow-growing bacillus still uncultiv ...

PUBLIC LIBRARY SCIENCE2021

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

Stewart Cole, Andrej Benjak, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien

The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of ac ...

2020

Worldwide, tuberculosis (TB) is the leading cause of death due to a single infectious agent, claiming 1.6 million human lives and causing >10 million new cases in 2017 alone, mostly in low-income regions. The intracellular pathogen Mycobacterium tuberculos ...

EPFL2019

The major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, ...

WILEY2019

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Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into g ...

2019

Tuberculosis (TB), whose etiological agent is Mycobacterium tuberculosis (M. tuberculosis), has plagued humanity since antiquity. Even with chemotherapy available today, TB is the leading cause of death due to an infectious disease. Modern day factors, suc ...

EPFL2018

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Nodular thelitis is a chronic enzootic infection affecting dairy cows and goats. The causative agent was recently shown to be related to the leprosy-causing bacilli Mycobacterium leprae and Mycobacterium lepromatosis. In this study, the genome of this path ...

AMER SOC MICROBIOLOGY2018