Publications de Gaëlle Séraphine Kolly

Promoter mutagenesis for fine-tuning expression of essential genes in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Gaëlle Séraphine Kolly

A range of regulated gene expression systems has been developed for mycobacteria in the last few years to facilitate the study of essential genes, validate novel drug targets and evaluate their vulnerability. Among these, the TetR/Pip-OFF repressible promo ...

Wiley2018

Rv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation

Stewart Cole, Claudia Sala, Andrej Benjak, Anthony Vocat, Gaëlle Séraphine Kolly, Andréanne Lupien, Nina Theres Odermatt

A handful of nucleoid-associated proteins (NAPs) regulate the vast majority of genes in a bacterial cell. H-NS, the histone-like nucleoid-structuring protein, is one of these NAPs and protects Escherichia coli from foreign gene expression. Though lacking a ...

American Society for Microbiology2017

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

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

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

Stewart Cole, Matteo Dal Peraro, Claudia Sala, Luciano Andres Abriata, Raju Mukherjee, Gaëlle Séraphine Kolly, Mahé Cécile Raccaud

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 ...

American Society for Microbiology2015

2-Carboxyquinoxalines Kill Mycobacterium tuberculosis through Noncovalent Inhibition of DprE1

Stewart Cole, Neeraj Dhar, Florence Pojer, Ruben Hartkoorn, Joao Pedro De Almeida Neres, Gaëlle Séraphine Kolly

Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 mu M, ...

American Chemical Society2015

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

Stewart Cole, Ruben Hartkoorn, Joao Pedro De Almeida Neres, Anthony Vocat, Trent Michael Conroy, Jérémie Piton, Gaëlle Séraphine Kolly

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 ...

American Society for Microbiology2015

DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization

Stewart Cole, Gaëlle Séraphine Kolly, Joao Pedro De Almeida Neres, Raju Mukherjee

The flavo-enzyme DprE1 catalyzes a key epimerization step in the decaprenyl-phosphoryl d-arabinose (DPA) pathway, which is essential for mycobacterial cell wall biogenesis and targeted by several new tuberculosis drug candidates. Here, using differential r ...

American Chemical Society2015

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

Stewart Cole, John McKinney, Claudia Sala, Neeraj Dhar, 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 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