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Publications associées (23)

Single-cell analysis of the interactions between Mycobacterium tuberculosis and macrophages

Ophélie Rutschmann

Mycobacterium Tuberculosis is a highly effective pathogen infecting nearly a third of the world's population. An M. tuberculosis infection starts when droplets containing bacteria enter an individual's lungs. The first host cells to contact the bacteria ar ...

EPFL2024

FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis

Stewart Cole, Claudia Sala

Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is the world's leading cause of death from an infectious disease. One of the main features of this pathogen is the complex and dynamic lipid composition of the cell envelope, which adap ...

Frontiers Media SA2020

Multicenter analysis of sputum microbiota in tuberculosis patients

Stewart Cole, Claudia Sala, Jacques Rougemont, Philippe Busso, Marion Leleu, Andrej Benjak

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship betweenM.tuberculos ...

2020

Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169)

Stewart Cole, Shi-Yan Caroline Foo, Anthony Vocat, Jean-Yves Gillon, Andréanne Lupien

The efficacy of the standardized four-drug regimen (comprising isoniazid, rifampin, pyrazinamide, and ethambutol) for the treatment of tuberculosis (TB) is menaced by the emergence of multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of ...

AMER SOC MICROBIOLOGY2018

Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives

Jacques Fellay, Nimisha Chaturvedi

Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable ...

2018

Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of Mycobacterium tuberculosis

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

New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis. We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agent ...

AMER SOC MICROBIOLOGY2018

Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression

Stewart Cole, Andrej Benjak

MmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalact ...

Nature Research2017

New 1-hydroxy-2-thiopyridine derivatives active against both replicating and dormant Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat

Tuberculosis (TB) treatment is confounded by the range of metabolic states displayed by Mycobacterium tuberculosis, by the long duration required and by the increasing prevalence of drug-resistant strains. Latent TB infection is especially difficult to tre ...

Elsevier Science Bv2017

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b

Stewart Cole, Claudia Sala, Swapna Uplekar, Ming Zhang, Andrej Benjak, Jérémie Piton

Background: The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during activ ...

2016

Stress and Host Immunity Amplify Mycobacterium tuberculosis Phenotypic Heterogeneity and Induce Nongrowing Metabolically Active Forms

John McKinney, Neeraj Dhar, Giulia Manina

Nonreplicating and metabolically quiescent bacteria are implicated in latent tuberculosis infections and relapses following "sterilizing" chemotherapy. However, evidence linking bacterial dormancy and persistence in vivo is largely inconclusive. Here we me ...

Cell Press2015

Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure-activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-beta-D-ribose 2 '-oxidase

Stewart Cole, Florence Pojer, Anirban Ghosh, Joao Pedro De Almeida Neres

We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of deca ...

Elsevier2015

4-Pyrimidinylamino-benzenesulfonamide derivatives and their use for the inhibition of polo-like kinase 1 (PLK1) for the treatment of cancer and their use for the treatment of bacterial infections

Stewart Cole, Ruben Hartkoorn, Edina Rita Székely

The present invention relates to 4-pyrimidinylamino-benzenesulfonamide derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, regioisomeric and polymorphic forms thereof, processes for manufacturing of them, the use o ...

2015

GtrA Protein Rv3789 Is Required for Arabinosylation of Arabinogalactan in Mycobacterium tuberculosis

Gaëlle Séraphine Kolly, Stewart Cole, Claudia Sala, Matteo Dal Peraro, Mahé Cécile Raccaud, Raju Mukherjee, Luciano Andres Abriata

Mycobacterium tuberculosis possesses a thick and highly hydrophobic cell wall principally composed of a mycolyl-arabinogalactan-peptidoglycan complex, which is critical for survival and virulence. DprE1 is a well-characterized component of decaprenyl-phosp ...

American Society for Microbiology2015

In Vitro and In Vivo Activities of Three Oxazolidinones against Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ming Zhang, Anthony Vocat

Oxazolidinones represent a new class of antituberculosis drugs that exert their function by inhibiting protein synthesis. Here, we compared the activities of three oxazolidinones, linezolid, PNU-100480, and AZD5847, against latent tuberculosis using a simp ...

Amer Soc Microbiology2014

EspI regulates the ESX-1 secretion system in response to ATP levels in Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Jeffrey Chen, Ming Zhang, Jan Lars Rybniker

The function of EspI, a 70kDa protein in Mycobacterium tuberculosis, has remained unclear. Although EspI is encoded by a gene within the esx-1 locus, in this study we clarify previous conflicting results and show that EspI is not essential for ESX-1-mediat ...

Wiley-Blackwell2014

Genetic analysis of the decaprenyl-phospho-D-arabinofuranose pathway in Mycobacterium tuberculosis

Gaëlle Séraphine Kolly

The tuberculosis (TB) epidemic still represents a major global health problem as it kills more than one million people every year. Africa and Asia are arguably the most affected regions due to the dramatic increase of TB cases in HIV-positive patients and ...

EPFL2014

Streptomycin-Starved Mycobacterium tuberculosis 18b, a Drug Discovery Tool for Latent Tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Ming Zhang

Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-sta ...

Amer Soc Microbiology2012

Detection and treatment of subclinical tuberculosis

Stewart Cole

Reduction of active disease by preventive therapy has the potential to make an important contribution towards the goal of tuberculosis (TB) elimination. This report summarises discussions amongst a Working Group convened to consider areas of research that ...

Elsevier2012

In Vitro Combination Studies of Benzothiazinone Lead Compound BTZ043 against Mycobacterium tuberculosis

Stewart Cole, Ruben Hartkoorn, Benoit Lechartier

Benzothiazinones (BTZ) are a new class of drug candidates to combat tuberculosis that inhibit decaprenyl-phosphoribose epimerase (DprE1), an essential enzyme involved in arabinan biosynthesis. Using the checkerboard method and cell viability assays, we hav ...

Amer Soc Microbiology2012

A Simple Model for Testing Drugs against Non-replicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Ming Zhang

Non-replicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against non-growing cell ...

2010

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