Publications de Stewart Cole | EPFL Graph Search

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An 86-year old female patient from northeast Mexico presented with diffuse lepromatous leprosy (DLL). Sequence analysis of four genes (rrs, rpoB, sigA and hsp65) from the skin biopsy identified Mycobacterium lepromatosis. This is the first independent conf ...

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 ...

We previously reported the synthesis and the antimycobacterial activity of 4-(7,7-dimethyl-7H-furo[3,2-f]chromen-2-yl)pyridine. From this result, we sought to design simple synthetic accesses to related structures allowing the preparation of a diverse set ...

In this work, the synthesis and the pharmacological evaluation of diphenoxyadamantane alkylamines Ia-f and IIa-f is described. The new diphenoxy-substituted adamantanes share structural features present in trypanocidal and antitubercular agents. 1-Methylpi ...

Mycobacterium tuberculosis (M. tb) the causative agent of tuberculosis (TB) causes 1.7 million deaths annually. According to the World Health Organization, in some areas of the world, 25% of TB cases are due to multi- or extensively drug resistant M. tb st ...

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 ...

Pathogenicity of Mycobacterium tuberculosis (M. tb) is mediated by the ESX-1 secretion system, which exports EsxA and EsxB, the major virulence factors that are co-secreted with EspA and EspC. Functional information about ESX-1 components is scarce. Here, ...

Mycobacterium leprae protein ML2640c belongs to a large family of conserved hypothetical proteins predominantly found in mycobacteria, some of them predicted as putative S-adenosylmethionine (AdoMet)-dependent methyltransferases (MTase). As part of a Struc ...

8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-beta-D-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studie ...

The expectation that genomics would result in new therapeutic interventions for infectious diseases remains unfulfilled. In the post-genomic era, the decade immediately following the availability of the genome sequence of Mycobacterium tuberculosis, tuberc ...

Background: Intrigued by the fact that aminoadamantane derivatives, bearing the active 1,2-ethylenediamine moiety, are promising antitubercular agents, we report herein the synthesis and the antitubercular evaluation of N,N'-substituded-4,4'-[adamantane-2, ...

The synthesis and preliminary pharmacological evaluation of new indole and adamantane amido derivatives is described. The design was based on the pharmacophoric properties of 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl), 6-[4-(trifluoro methoxy)phenyl ...

Background: Clostridium botulinum and related clostridia express extremely potent toxins known as botulinum neurotoxins (BoNTs) that cause severe, potentially lethal intoxications in humans. These BoNT-producing bacteria are categorized in seven major toxi ...

During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We fou ...

There is an urgent need to discover new antitubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that ...

The cell envelope of Mycobacterium tuberculosis contains glycans and lipids of peculiar structure that play prominent roles in the biology and pathogenesis of tuberculosis. Consequently, the chemical structure and biosynthesis of the cell wall have been in ...

ESAT-6 system 1 (ESX-1)-mediated secretion in Mycobacterium tuberculosis is dependent on proteins encoded by the cotranscribed espA-espC-espD gene cluster. While the roles of EspA and EspC with respect to the ESX-1 secretion system have been actively inves ...

The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal ...

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 ...

Stewart Cole

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A Case of Diffuse Lepromatous Leprosy associated with Mycobacterium lepromatosis

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

Diversity-oriented synthesis of furo[3,2-f]chromanes with antimycobacterial activity

Synthesis of diphenoxyadamantane alkylamines with pharmacological interest

Towards anti-virulence drugs targeting ESX-1 mediated pathogenesis of Mycobacterium tuberculosis

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

EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion

The crystal structure of M. leprae ML2640c defines a large family of putative S-adenosylmethionine-dependent methyltransferases in mycobacteria

The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis

Tuberculosis drug discovery in the post-post-genomic era

Synthesis of Adamantane Aminoethers with Antitubercular Potential

Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest

Application of High-Density DNA Resequencing Microarray for Detection and Characterization of Botulinum Neurotoxin-Producing Clostridia

NOS2-deficient mice with hypoxic necrotizing lung lesions predict outcomes of tuberculosis chemotherapy in humans

Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria

The Phosphatidyl-myo-Inositol Mannosyltransferase PimA Is Essential for Mycobacterium tuberculosis Growth In Vitro and In Vivo

EspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis

Evaluation of Auramine O staining and conventional PCR for leprosy diagnosis: A comparative cross-sectional study from Ethiopia

Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence

Towards a new combination therapy for tuberculosis with next generation benzothiazinones