Publications de Jan Lars Rybniker

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

Stewart Cole, Kai Johnsson, John McKinney, Graham Knott, Neeraj Dhar, Ruben Hartkoorn, Isabella Santi, Anthony Vocat, Gaëlle Séraphine Kolly, Monica Rengifo Gonzalez

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 ...

Wiley-Blackwell2017

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

Stewart Cole, Claudia Sala, Jan Lars Rybniker, Ye Lou

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, ...

2017

Characterization of DprE1-Mediated Benzothiazinone Resistance in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Stefanie Boy-Röttger, Joao Pedro De Almeida Neres, Benoit Lechartier, Jérémie Piton, Gaëlle Séraphine Kolly, Jan Lars Rybniker, Shi-Yan Caroline Foo, Andréanne Lupien

Benzothiazinones (BTZs) are a class of compounds found to be extremely potent against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains. The potency of BTZs is explained by their specificity for their target decaprenylphosphoryl-D ...

American Society for Microbiology2016

Benzothiophene, benzyloxybenzylidene and indoline derivatives useful for the treatment of tuberculosis

Stewart Cole, Jan Lars Rybniker

The present invention relates to benzothiophene, benzyloxybenzylidene and indoline-2-one derivatives and the use of said derivatives in the treatment and/or prevention of tuberculosis. ...

2016

Benzimidazole sulfide derivatives for the treatment or prevention of tuberculosis

Stewart Cole, Jan Lars Rybniker

The present invention relates to the use of benzimidazole sulfide derivatives and prodrugs thereof in the treatment and/or prevention of tuberculosis. ...

2016

Lansoprazole is an antituberculous prodrug targeting cytochrome bc1

Stewart Cole, Florence Pojer, Claudia Sala, Andrej Benjak, Anthony Vocat, Philippe Busso, Jan Lars Rybniker

Better antibiotics capable of killing multi-drug-resistant Mycobacterium tuberculosis are urgently needed. Despite extensive drug discovery efforts, only a few promising candidates are on the horizon and alternative screening protocols are required. Here, ...

Nature Publishing Group2015

Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1

Stewart Cole, Andrea Ablasser, Claudia Sala, Muhammet Fatih Gülen, Sonia Garcia Perin, Ye Lou, Jan Lars Rybniker

Cytosolic detection of microbial products is essential for the initiation of an innate immune response against intracellular pathogens such as Mycobacterium tuberculosis (Mtb). During Mtb infection of macrophages, activation of cytosolic surveillance pathw ...

Cell Press2015

The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron sulfur cluster biogenesis and oxidative stress defence

Stewart Cole, Florence Pojer, Gaëlle Séraphine Kolly, Jan Lars Rybniker, Jeffrey Chen

The complex multiprotein systems for the assembly of protein-bound iron sulfur (Fe S) clusters are well defined in Gram-negative model organisms. However, little is known about Fe S cluster biogenesis in other bacterial species. The ISC (iron sulfur cluste ...

Portland Press2014

Anticytolytic Screen Identifies Inhibitors of Mycobacterial Virulence Protein Secretion

Stewart Cole, Claudia Sala, Ruben Hartkoorn, Andrej Benjak, Ming Zhang, Anthony Vocat, 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

Tuberculosis drug discovery in the post-post-genomic era

Stewart Cole, Benoit Lechartier, Jan Lars Rybniker

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 ...

Wiley Open Access2014