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Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis

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Whole cell screen based identification of spiropiperidines with potent antitubercular properties

Stewart Cole, Ruben Hartkoorn

Whole cell based screens to identify hits against Mycobacterium tuberculosis (Mtb), carried out under replicating and non-replicating (NRP) conditions, resulted in the identification of multiple, novel but structurally related spiropiperidines with potent ...

Elsevier2015

Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis

Stewart Cole, Benoit Lechartier

Clofazimine (CZM) is an antileprosy drug that was recently repurposed for treatment of multidrug-resistant tuberculosis. In Mycobacterium tuberculosis, CZM appears to act as a prodrug, which is reduced by NADH dehydrogenase (NDH-2), to release reactive oxy ...

Amer Soc Microbiology2015

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

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The antileprosy drug clofazimine is also of interest for the treatment of multidrug-resistant tuberculosis. To understand possible resistance mechanisms, clofazimine-resistant Mycobacterium tuberculosis mutants were isolated in vitro, and, unexpectedly, fo ...

Amer Soc Microbiology2014

On using the streptomycin-starved 18b strain as a model for nonreplicating Mycobacterium tuberculosis, we identified a 5-nitrothiophene compound as highly active but not cytotoxic. Mutants resistant to 5-nitrothiophenes were found be cross-resistant to the ...

Amer Soc Microbiology2014

New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects

Stewart Cole

About 1.3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex r ...

Elsevier Science Inc2014

Phenotypic Profiling of Mycobacterium tuberculosis EspA Point Mutants Reveals that Blockage of ESAT-6 and CFP-10 Secretion In Vitro Does Not Always Correlate with Attenuation of Virulence

Stewart Cole, Neeraj Dhar, Florence Pojer, Ming Zhang, Jan Lars Rybniker, Jeffrey Chen, Anna De Graff Tischler

The EspA protein of Mycobacterium tuberculosis is essential for the type VII ESX-1 protein secretion apparatus, which delivers the principal virulence factors ESAT-6 and CFP-10. In this study, site-directed mutagenesis of EspA was performed to elucidate it ...

American Society for Microbiology2013

Identification of a small molecule with activity against drug-resistant and persistent tuberculosis

Jian Wang, Yi Zhang, Claudia Trefzer, Ji Hyun Kim

A cell-based phenotypic screen for inhibitors of biofilm formation in mycobacteria identified the small molecule TCA1, which has bactericidal activity against both drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb) and sterilizes Mtb in vitro ...

National Academy of Sciences2013

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The transketolase (TKT) enzyme in Mycobacterium tuberculosis represents a novel drug target for tuberculosis treatment and has low homology with the orthologous human enzyme. Here, we report on the structural and kinetic characterization of the transketola ...

Royal Soc2012

Decaprenylphosphoryl-beta-D-Ribose 2 '-Epimerase from Mycobacterium tuberculosis is a Magic Drug Target

Giulia Manina

Tuberculosis is still a leading cause of death in developing countries and a resurgent disease in developed countries. The selection and soaring spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-T ...

2010