Stewart Cole

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Mechanism of Action of 5-Nitrothiophenes against Mycobacterium tuberculosis

Stewart Cole, Ruben Hartkoorn

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

Functional Dissection of Intersubunit Interactions in the EspR Virulence Regulator of Mycobacterium tuberculosis

Stewart Cole, Giovanni Dietler, Matteo Dal Peraro, Florence Pojer, Marco Stenta, Aleksandre Japaridze, Benjamin Blasco, Basile Isidore Martin Wicky

The nucleoid-associated protein EspR, a chromosome organizer, has pleiotropic effects on expression of genes associated with cell wall function and pathogenesis in Mycobacterium tuberculosis. In particular, EspR binds to several sites upstream of the espAC ...

Amer Soc Microbiology2014

Rv2466c Mediates the Activation of TP053 To Kill Replicating and Non-replicating Mycobacterium tuberculosis

Stewart Cole, Ruben Hartkoorn, Anthony Vocat

The emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis highlights the need to discover new antitubercular agents. Here we describe the synthesis and characterization of a new series of thienopyrimidine (TP) compoun ...

American Chemical Society2014

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

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

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

Anticytolytic Screen Identifies Inhibitors of Mycobacterial Virulence Protein Secretion

Stewart Cole, Claudia Sala, Ruben Hartkoorn, Andrej Benjak, Anthony Vocat, Ming Zhang, Jan Lars Rybniker, Jeffrey Chen, Edina Rita Székely

Mycobacterium tuberculosis (Mtb) requires protein secretion systems like ESX-1 for intracellular survival and virulence. The major virulence determinant and ESX-1 substrate, EsxA, arrests phagosome maturation and lyses cell membranes, resulting in tissue d ...

Cell Press2014

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The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) a ...

2014

Assessing the essentiality of the decaprenyl-phospho-D-arabinofuranose pathway in Mycobacterium tuberculosis using conditional mutants

Stewart Cole, John McKinney, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Gaëlle Séraphine Kolly

In Mycobacterium tuberculosis the decaprenyl-phospho-d-arabinofuranose (DPA) pathway is a validated target for the drugs ethambutol and benzothiazinones. To identify other potential drug targets in the pathway, we generated conditional knock-down mutants o ...

Wiley-Blackwell2014

The Phosphatidyl-myo-Inositol Mannosyltransferase PimA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo (vol 196, pg 3441, 2014)

Stewart Cole, Neeraj Dhar, Claudia Sala, Ming Zhang, Gaëlle Séraphine Kolly, Naveen Kumar

American Society for Microbiology2014

The Crystal Structures of Apo and cAMP-Bound GlxR from Corynebacterium glutamicum Reveal Structural and Dynamic Changes upon cAMP Binding in CRP/FNR Family Transcription Factors

Stewart Cole, Florence Pojer

The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator) transcriptional regulators that play central roles in ...

Public Library of Science2014