Publications related to Cross-Resistance between Clofazimine and Bedaquiline through Upregulation of MmpL5 in Mycobacterium tuberculosis

Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania

The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aim ...

Nature Portfolio2024

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

Ophélie Rutschmann

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

Human alveolar lining fl uid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells

Vivek Vijay Thacker, Richa Mishra

The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis ( M.tb ) that kills one person every 18 seconds. Once M.tb reaches the ...

Elsevier Science Inc2024

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

Host-Pathogen Interactions Through the Genomic Lens

Zhi Ming Xu

Hosts and pathogens are involved in a long-standing evolutionary arms race characterized by successive rounds of evolution. Specifically, while hosts evolve resistance against infections, pathogens adapt to re-establish virulence. Since the signatures of t ...

EPFL2023

Preexisting Heterogeneity of Inducible Nitric Oxide Synthase Expression Drives Differential Growth of Mycobacterium tuberculosis in Macrophages

John McKinney, Ophélie Rutschmann, Chiara Toniolo

Mycobacterium tuberculosis infection is initiated by the inhalation and implantation of bacteria in the lung alveoli, where they are phagocytosed by macrophages. Even a single bacterium may be sufficient to initiate infection. Thereafter, the clinical outc ...

AMER SOC MICROBIOLOGY2022

Development and validation of a multiplex real-time qPCR assay using GMP-grade reagents for leprosy diagnosis

Stewart Cole, Charlotte Avanzi, Thyago Leal Calvo

Author summaryLeprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, an obligate intracellular bacterium. Diagnosis of leprosy often relies on skin examinations for clinical signs, bacilli staining from skin smears and invasive s ...

PUBLIC LIBRARY SCIENCE2022

A new paradigm for leprosy diagnosis based on host gene expression

Stewart Cole, Philippe Busso, Andrej Benjak, Charlotte Avanzi, Thyago Leal Calvo

Author summary ...

PUBLIC LIBRARY SCIENCE2021

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

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

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

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

Stewart Cole, Claudia Sala

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

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

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment

Stewart Cole, Philippe Busso, Andrej Benjak, Charlotte Avanzi

A case of Mycobacterium leprae rifampin resistance after irregular antile- prosy treatments since 1971 is reported. Whole-genome sequencing from four longi- tudinal samples indicated relapse due to acquired rifampin resistance and not to re- infection with ...

AMER SOC MICROBIOLOGY2020

Time-lapse high-resolution microscopy to study the morphogenesis of microorganisms

Mélanie Thérèse Marie Hannebelle

Mycobacterium tuberculosis, the etiological agent for the tuberculosis disease, is a bacterial pathogen thought to infect about a quarter of the global human population. It is the first cause of death among infectious diseases, and is most prevalent in low ...

EPFL2020

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

Do chance encounters between heterogeneous cells shape the outcome of tuberculosis infections?

John McKinney, Ophélie Rutschmann, Chiara Toniolo

The sum of all of the interactions between single bacteria and host cells determines if an infection is cleared, controlled, or progresses at the whole host-organism level. These individual interactions have independent trajectories defined by diverse and ...

2020

Genomic Characterization of Mycobacterium lepraeto Explore Transmission Patterns Identifies New Subtype in Bangladesh

Stewart Cole, Andrej Benjak, Charlotte Avanzi

Mycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. In 2001, the genome ofM. lepraewas first described and subsequently ...

Frontiers Media SA2020