Publications associées à Leads for antitubercular compounds from kinase inhibitor library screens

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

Methods for high-throughput synthesis and screening of peptide libraries

Zsolt Bognár

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

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

Microfluidic systems for infectious disease diagnostics

Thomas Lehnert, Martinus Gijs

Microorganisms, encompassing both uni- and multicellular entities, exhibit remarkable diversity as omnipresent life forms in nature. They play a pivotal role by supplying essential components for sustaining biological processes across diverse ecosystems, i ...

Royal Soc Chemistry2024

Homogeneous vs. heterogeneous photo-Fenton elimination of antibiotic-resistant bacteria bearing intracellular or extracellular resistance: Do resistance mechanisms interfere with disinfection pathways?

César Pulgarin, Stefanos Giannakis, Truong-Thien Melvin Le, Jérémie Decker

The present study aimed to fill the knowledge gap between the implications of intracellular and extracellular antibiotic resistance mechanisms may inflict on the inactivation pathways of the photo-Fenton process under mild conditions. It was thus designed ...

Elsevier Sci Ltd2024

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

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers

Camila Bacellar Cases Da Silveira, Christoph Bostedt

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Nature Portfolio2023

Development of methods for the synthesis of large combinatorial libraries of macrocyclic compounds

Mischa Schüttel

Macrocycles have raised much interest in the pharmaceutical industry due to their ability to bind challenging targets while often still being able to cross membranes to reach intracellular proteins. However, the development of macrocyclic ligands to new di ...

EPFL2023

Generating macrocyclic inhibitors of protein-protein interactions

Gontran Sangouard

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

EPFL2022

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

Identification of genes required for host-cell adhesion and antibiotic persistence of uropathogenic Escherichia coli via high-content screening

Thomas Marie Simonet

Uropathogenic Escherichia coli (UPEC) are the most common bacterial pathogens causing urinary tract infections (UTIs). Driven by the development of antibiotic resistant UPEC strains, UTIs have become a major public health issue and generate substantial hea ...

EPFL2022

Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale

Gerardo Turcatti, Jonathan Patrice Vesin, Christian Heinis, Alessandro Angelini, Gontran Sangouard, Julien Bortoli Chapalay, Mischa Schüttel, Ganesh Kumar Mothukuri, Manuel Leonardo Merz, Sevan Mleh Habeshian, Cristina Diaz Perlas, Zsolt Bognár

Macrocycles have excellent potential as therapeutics due to their ability to bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, ...

Nature Research2022

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, i ...

EPFL2022

Spatial analysis of the Healthy Built Environment: an application on Cardiovascular Risk Factors in the canton of Geneva

Andrea Salmi

Most of the world population lives in urban areas, the share of the urban population is estimated to increase in the future decades. The complexity of different land uses and services in urban areas, which composes the built environment, influences human h ...

EPFL2022

High-content, arrayed compound screens with rhinovirus, influenza A virus and herpes simplex virus infections

Gerardo Turcatti, Fabien Kuttler

Viruses are genetically and structurally diverse, and outnumber cells by orders of magnitude. They can cause acute and chronic infections, suppress, or exacerbate immunity, or dysregulate survival and growth of cells. To identify chemical agents with pro- ...

2022

Image- and Fluorescence-Based Test Shows Oxidant-Dependent Damages in Red Blood Cells and Enables Screening of Potential Protective Molecules

Gerardo Turcatti, Michel Prudent, Benjamin Rappaz, Manon Sandra Bardyn, David Crettaz

An increase of oxygen saturation within blood bags and metabolic dysregulation occur during storage of red blood cells (RBCs). It leads to the gradual exhaustion of RBC antioxidant protective system and, consequently, to a deleterious state of oxidative st ...

2021

Microfluidic Platforms for the Study of Bacterial Metabolism and Antimicrobial Susceptibility Testing

Yang Liu

Fast spreading antimicrobial resistance (AMR) is an emerging major public health issue. New therapeutic and diagnostic paradigms must be implemented to counteract this evolution. In this respect, fast antimicrobial susceptibility testing (AST) plays an imp ...

EPFL2021

NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism

Vassily Hatzimanikatis, Noushin Hadadi, Jasmin Maria Hafner, Anush Chiappino-Pepe, Homa Mohammadi Peyhani

The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...

2021