Publications de Jan Lars Rybniker

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

Kai Johnsson, Gaëlle Séraphine Kolly, Graham Knott, John McKinney, Stewart Cole, Neeraj Dhar, Monica Rengifo Gonzalez, Ruben Hartkoorn, Isabella Santi, Edina Rita Székely, François Signorino-Gelo, Jan Lars Rybniker, Anthony Vocat

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

Gaëlle Séraphine Kolly, Stewart Cole, Claudia Sala, Benoit Lechartier, Joao Pedro De Almeida Neres, Stefanie Boy-Röttger, Jan Lars Rybniker, Shi-Yan Caroline Foo, Jérémie Piton, 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, Claudia Sala, Florence Pojer, Philippe Busso, Jan Lars Rybniker, Anthony Vocat, Andrej Benjak

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

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

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

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

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

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

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

Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent virulence

Stewart Cole, Neeraj Dhar, Florence Pojer, Jeffrey Chen, Ming Zhang, Stefanie Boy-Röttger, Jan Lars Rybniker

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 ...

Wiley-Blackwell2013

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

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