Publications de Claudia Sala | EPFL Graph Search

Advanced Quantification Methods To Improve the 18b Dormancy Model for Assessing the Activity of Tuberculosis Drugs In Vitro

One of the reasons for the lengthy tuberculosis (TB) treatment is the difficulty to treat the nonmultiplying mycobacterial subpopulation. In order to assess the ability of (new) TB drugs to target this subpopulation, we need to incorporate dormancy models ...

AMER SOC MICROBIOLOGY2020

FasR Regulates Fatty Acid Biosynthesis and Is Essential for Virulence of Mycobacterium tuberculosis

Stewart Cole, Claudia Sala

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 SA2020

Polarly Localized EccE(1) Is Required for ESX-1 Function and Stabilization of ESX-1 Membrane Proteins in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Ming Zhang, Jérémie Piton, Paloma Julia Soler Arnedo

Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialized ESX-1 secretion system to secrete virulence factors and potent im ...

American Society for Microbiology2020

Multicenter analysis of sputum microbiota in tuberculosis patients

Stewart Cole, Claudia Sala, Jacques Rougemont, Philippe Busso, Marion Leleu, Andrej Benjak

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship betweenM.tuberculos ...

2020

Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Andrej Benjak, Nina Theres Odermatt

Tight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, ...

Nature Research2018

EspL is essential for virulence and stabilizes EspE, EspF and EspH levels in Mycobacterium tuberculosis

Stewart Cole, Claudia Sala, Andrej Benjak, Nina Theres Odermatt, Sofia Ulrika Magnusdotter Von Schultz, Paloma Julia Soler Arnedo

The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis, one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 1 ...

PUBLIC LIBRARY SCIENCE2018

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

Gaëlle Séraphine Kolly, Stewart Cole, Claudia Sala

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

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

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

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

The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis

John McKinney, Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Raphael Christopher Sommer, Anthony Vocat, Andréanne Lupien

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 Soc2017

Transcription facilitated genome-wide recruitment of topoisomerase I and DNA gyrase

Stewart Cole, Claudia Sala, Wareed Ahmed

Movement of the transcription machinery along a template alters DNA topology resulting in the accumulation of supercoils in DNA. The positive supercoils generated ahead of transcribing RNA polymerase (RNAP) and the negative supercoils accumulating behind i ...

Public Library Science2017

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b

Stewart Cole, Claudia Sala, Swapna Uplekar, Ming Zhang, Andrej Benjak, Jérémie Piton

Background: The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during activ ...

2016

Mycobacterium ulcerans Mouse Model Refinement for Pre-Clinical Profiling of Vaccine Candidates

Claudia Sala

Buruli Ulcer is a neglected tropical disease leading to extensive disabilities and morbidity in West Africa. In this paper we sought to characterize various strains of Mycobacterium ulcerans (M. ulcerans) with different origins and laboratory passage recor ...

Public Library of Science2016

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

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

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

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

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

Bioluminescence for Assessing Drug Potency against Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Ming Zhang, Benoit Lechartier, Anthony Vocat

Targeting dormant Mycobacterium tuberculosis represents a challenge to antituberculosis drug discovery programs. We previously reported and validated the use of the streptomycin (STR)-dependent M. tuberculosis 18b strain as a tool for assessing drug potenc ...

American Society for Microbiology2015

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

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

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

Gaëlle Séraphine Kolly, Stewart Cole, Neeraj Dhar, Claudia Sala, Ming Zhang, Naveen Kumar

The cell envelope of Mycobacterium tuberculosis contains glycans and lipids of peculiar structure that play prominent roles in the biology and pathogenesis of tuberculosis. Consequently, the chemical structure and biosynthesis of the cell wall have been in ...

American Society for Microbiology2014