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

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Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria

Paul Joseph Dyson, Stewart Cole, John McKinney, Neeraj Dhar, Thierry Laroche, Jérémie Piton, Joao Pedro De Almeida Neres, Raphael Christopher Sommer, Raju Mukherjee

Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaf ...

2018

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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 ...

Amer Soc Microbiology2017

MmpL3 is an inner membrane transporter of Mycobacterium tuberculosis responsible for the export of trehalose momomycolate, a precursor of the mycobacterial outer membrane component trehalose dimycolate (TDM), as well as mycolic acids bound to arabinogalact ...

Nature Publishing Group2017

An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division

Neeraj Dhar, Ashima Bhaskar, Dong Li

Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell div ...

Nature Publishing Group2017

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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

Mycobacterium tuberculosis requires the phosphate-sensing signal transduction system Pst/SenX3-RegX3 to resist host immune responses. A Delta pstA1 mutant lacking a Pst phosphate uptake system component is hypersensitive to diverse stress conditions in vit ...

American Society for Microbiology2016

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro gr ...

Wiley-V C H Verlag Gmbh2016

Mechanistic insight into mycobacterial MmpL protein function

Stewart Cole, Edina Rita Székely

Mycobacterial cell walls are complex structures containing a broad range of unusual lipids, glycolipids and other polymers, some of which act as immunomodulators or virulence determinants. Better understanding of the enzymes involved in export processes wo ...

Wiley-Blackwell2016

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

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

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

Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG

Stewart Cole, Ruben Hartkoorn

To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against M. tuberculosi ...

Elsevier2015