Publications associées à EspD Is Critical for the Virulence-Mediating ESX-1 Secretion System in Mycobacterium tuberculosis

Single-cell analysis of the interactions between Mycobacterium tuberculosis and macrophages

Mycobacterium Tuberculosis is a highly effective pathogen infecting nearly a third of the world's population. An M. tuberculosis infection starts when droplets containing bacteria enter an individual's lungs. The first host cells to contact the bacteria ar ...

EPFL2024

Investigating the composition and recruitment of the mycobacterial ImuA'-ImuB-DnaE2 mutasome

John McKinney, Neeraj Dhar, Zela Alexandria-Mae Martin

A DNA damage-inducible mutagenic gene cassette has been implicated in the emergence of drug resistance in Mycobacterium tuberculosis during anti-tuberculosis (TB) chemotherapy. However, the molecular composition and operation of the encoded 'mycobacterial ...

Elife Sciences Publ Ltd2023

Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania

Jacques Fellay, Zhi Ming Xu

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC populat ...

PUBLIC LIBRARY SCIENCE2023

Real-time monitoring of single-cell secretion with a high-throughput nanoplasmonic microarray

Hatice Altug, Xiaokang Li, Yen-Cheng Liu, Eduardo Romero Arvelo, Saeid Ansaryan

Proteins secreted by cells play significant roles in mediating many physiological, developmental, and pathological processes due to their functions in intra/intercellular communication and signaling. Conventional end-point methods are insufficient for unde ...

Elsevier2022

High resolution CryoEM structure of the ring-shaped virulence factor EspB from Mycobacterium tuberculosis

Stewart Cole, Florence Pojer, Jérémie Piton

The EspB protein of Mycobacterium tuberculosis is a 60 kDa virulence factor, implicated in conjugation and exported by the ESX-1 system of which it may also be a component. Previous attempts to obtain high-resolution maps of EspB by cryo-electron microscop ...

2020

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

Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin

Stewart Cole, Ruben Hartkoorn, Anthony Vocat

A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond foun ...

AMER CHEMICAL SOC2020

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

New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis

Stewart Cole, Shi-Yan Caroline Foo, Anthony Vocat, Andrej Benjak, Jérémie Piton, Andréanne Lupien

The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of ac ...

2020

Label-free plasmonic biosensors for real-time live cell analysis

Xiaokang Li

For decades, the understanding of life has been focused on its most fundamental building blocks: molecules. Deciphering the dynamic activities of protein molecules in human cells is of vital significance for fundamental and clinical studies. The minuscule ...

EPFL2019

Single-cell studies of Mycobacterium smegmatis cell cycle using time-lapse fluorescence microscopy

Joëlle Xiao Yuan Ven

Cell division is one of the most primordial cellular processes and is essential for life propagation. It is composed of crucial events, namely genome duplication, chromosomes segregation and membrane separation. Failure of these processes will have dramati ...

EPFL2019

Preexisting variation in DNA damage response predicts the fate of single mycobacteria under stress

John McKinney, Neeraj Dhar, Giulia Manina, Lalit Kumar Singh

Clonal microbial populations are inherently heterogeneous, and this diversification is often considered as an adaptation strategy. In clinical infections, phenotypic diversity is found to be associated with drug tolerance, which in turn could evolve into g ...

2019

A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria

Giovanni Dietler, Sandor Kasas, Giovanni Longo, Leonardo Venturelli

The development of antibiotic-resistant bacteria is a worldwide health-related emergency that calls for new tools to study the bacterial metabolism and to obtain fast diagnoses. Indeed, the conventional analysis time scale is too long and affects our abili ...

AMER SOC MICROBIOLOGY2019

Monitoring Tuberculosis Drug Activity in Live Animals by Using Near-Infrared Fluorescence Imaging

Stewart Cole, Raphael Christopher Sommer

Worldwide, tuberculosis (TB) is the leading cause of death due to infection with a single pathogenic agent, Mycobacterium tuberculosis. In the absence of an effective vaccine, new, more powerful antibiotics are required to halt the growing spread of multid ...

AMER SOC MICROBIOLOGY2019

Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG

Georg Fantner, Haig Alexander Eskandarian

The major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, ...

2019

Synthesis, biology, computational studies and in vitro controlled release of new isoniazid-based adamantane derivatives

Stewart Cole, Anthony Vocat

Aim: There is a necessity for new drugs to be more efficient than today's standard due to the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) Results/methodology: 12 new isoniazid-based adamantane derivatives were synthesized and te ...

FUTURE SCI LTD2019

Functional characterization of the virulence determinant ESX-1 from Mycobacterium tuberculosis

Paloma Julia Soler Arnedo

Tuberculosis (TB) is a chronic infectious disease that mainly affects the lungs and causes extensive human morbidity and mortality. It results from infection with Mycobacterium tuberculosis, a slow-growing intracellular pathogen that can replicate and surv ...

EPFL2018

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

A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK

Stewart Cole

Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new ...

Nature Research2018

Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2

Alexiane Clara Decout

Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and underst ...

Nature Research2018