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Cholesterol Catabolism by Mycobacterium tuberculosis Requires Transcriptional and Metabolic Adaptations
Related publications (45)
Mitochondrial respiratory chain dysfunction disrupts intracellular cholesterol homeostasis
Mitochondrial diseases are rare and severe conditions with debilitating symptoms. Biochemical defects in mitochondria however are common. The difference between these two frequencies is suspected to lie in the capability of the cells to adapt to the homeos ...
EPFL2022FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis
Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, is the world's leading cause of death from an infectious disease. One of the main features of this pathogen is the complex and dynamic lipid composition of the cell envelope, which adap ...
FRONTIERS MEDIA SA2020Mechanistic insights into AMP-activated protein kinase-dependent gene expression
AMP-activated protein kinase (AMPK) is a fundamental enzyme that controls energy homeostasis, through orchestrating the cellular response to a reduction in energy availability. Under conditions of cellular energy stress AMPK senses the decrease in ATP leve ...
EPFL2019Quantitative single cell dynamics of signaling and transcriptional response in mammalian cells
Cells live in ever-changing environments, thereby facing a variety of dynamic environmental signals. Environmental stimuli elicit intracellular responses through signaling pathways, which converge on transcriptional activation or repression of target genes ...
EPFL2018Functional Characterization of Nucleoid Associated Proteins Acting as Global Transcription Factors in Mycobacterium tuberculosis
The fatal lung disease tuberculosis is caused by the airborne Mycobacterium tuberculosis, a versatile pathogen adapted to rapidly changing environments. Instead of being eradicated by phagocytic cells of its human host, bacilli tune macrophages to support ...
EPFL2017The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis
Stewart Cole, John McKinney, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Anthony Vocat, Andréanne Lupien, Raphael Christopher Sommer
VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of a 15344-compound library. Sequencing of a VCC234718-resistant mutant identified a Y487C substitution in the inosine mo ...
Amer Chemical Soc2017Identification of the ER-resident E3 ubiquitin ligase RNF145 as a novel LXR-regulated gene
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol l ...
2017Identification 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, Anthony Vocat, Gaëlle Séraphine Kolly, Jan Lars Rybniker, Edina Rita Székely, François Signorino-Gelo, Isabella Santi, 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-Blackwell2017Phase specific transcriptional regulation of circadian clock and metabolism in mouse liver
The molecular clock has been conserved from cyanobacteria to mammals and is believed to align behavioral and biochemical processes with the diurnal cycle. This cellular mechanism has been an advantage to increase the fitness of organisms through the abilit ...
EPFL2016Mechanistic 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