A5078142118- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Immunodeficiency and Autoimmune Disorders
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Bacteriophages and microbial interactions
- Hepatitis C virus research
- Infectious Diseases and Tuberculosis
- Pharmacological Effects of Natural Compounds
- Cell Image Analysis Techniques
- vaccines and immunoinformatics approaches
- Antibiotic Resistance in Bacteria
- Diagnosis and treatment of tuberculosis
- Mosquito-borne diseases and control
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Immune responses and vaccinations
- Bacterial Genetics and Biotechnology
- Immune Response and Inflammation
- Liver Disease Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Viral Infections and Outbreaks Research
Centre National de la Recherche Scientifique
2016-2025
Inserm
2016-2025
Center for Infection and Immunity of Lille
2016-2025
Centre Hospitalier Universitaire de Lille
2016-2025
Institut Pasteur de Lille
2016-2025
Université de Lille
2016-2025
Institut Pasteur
2004-2021
Institut Pasteur Korea
2007-2017
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers
2016
Université d'Angers
2016
Tat is an 86-amino acid protein involved in the replication of human immunodeficiency virus type 1 (HIV-1). Several studies have shown that exogenous was able to translocate through plasma membrane and reach nucleus transactivate viral genome. A region centered on a cluster basic amino acids has been assigned this translocation activity. Recent data demonstrated chemical coupling Tat-derived peptide (extending from residues 37 72) several proteins allowed their functional internalization...
The distribution of 20 variable regions resulting from insertion-deletion events in the genomes tubercle bacilli has been evaluated a total 100 strains Mycobacterium tuberculosis , africanum canettii microti and bovis . This approach showed that majority these polymorphisms did not occur independently different M. complex but, rather, resulted ancient, irreversible genetic common progenitor strains. Based on presence or absence an specific deletion (TbD1), tuberculosi s can be divided into...
Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or microti, the vole bacillus, molecular basis for avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series chromosomal deletions common to both virulent and avirulent species but only single locus, RD1, that deleted from M. microti. Restoration by gene knock-in, resulted in marked change colonial morphology towards tubercle...
New drugs are required to counter the tuberculosis (TB) pandemic. Here, we describe synthesis and characterization of 1,3-benzothiazin-4-ones (BTZs), a new class antimycobacterial agents that kill Mycobacterium in vitro, ex vivo, mouse models TB. Using genetics biochemistry, identified enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase as major BTZ target. Inhibition this enzymatic activity abolishes formation decaprenylphosphoryl arabinose, key precursor is for cell-wall arabinans, thus...
ABSTRACT The 6-kDa early secreted antigenic target ESAT-6 and the 10-kDa culture filtrate protein CFP-10 of Mycobacterium tuberculosis are by ESX-1 system into host cell thereby contribute to pathogenicity. Although different studies performed at organismal cellular levels have helped explain ESX-1-associated phenomena, not much is known about how pathogenesis molecular level. In this study we describe interaction both proteins with lipid bilayers, using biologically relevant liposomal...
A critical feature of Mycobacterium tuberculosis, the causative agent human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing intracellular tubercle bacilli a key requirement efficient treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques lack validated targets. Here, we present development phenotypic cell-based assay that uses automated confocal...
CITATION: Bitter, W., et al. 2009. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathogens, 5(10): 1-6, doi: 10.1371/journal.ppat.1000507.
Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two the most widely used attenuated history research are Mycobacterium bovis BCG (BCG) H37Ra (H37Ra), which both during vitro serial passage. Whereas attenuation due mainly loss ESAT-6 secretion system, ESX-1, reason why remained unknown. However, here we show point mutation (S219L) predicted DNA...
Mycobacterium tuberculosis (Mtb) uses efficient strategies to evade the eradication by professional phagocytes, involving—as recently confirmed—escape from phagosomal confinement. While Mtb determinants, such as ESX-1 type VII secretion system, that contribute this phenomenon are known, host cell factors governing important biological process yet unexplored. Using a newly developed flow-cytometric approach for Mtb, we show macrophages expressing bivalent cation transporter Nramp-1, much less...
The dedicated secretion system ESX-1 of Mycobacterium tuberculosis encoded by the extended RD1 region (extRD1) assures export ESAT-6 protein and its partner, 10-kDa culture filtrate CFP-10, is missing from vaccine strains M. bovis BCG microti. Here, we systematically investigated involvement each individual gene in both antigens, specific immunogenicity, virulence. ESX-1-complemented microti were more efficiently engulfed bone-marrow-derived macrophages than controls, this may account for...
The role of biofilms in the pathogenesis mycobacterial diseases remains largely unknown. Mycobacterium ulcerans, etiological agent Buruli ulcer, a disfiguring disease humans, adopts biofilm-like structure vitro and vivo, displaying an abundant extracellular matrix (ECM) that harbors vesicles. composition ECM differs from classical found other bacterial biofilms. More than 80 proteins are present within this compartment appear to be involved stress responses, respiration, intermediary...
The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis over 11,000 Mycobacterium tuberculosis mutants. This very stringent makes use fluorescent staining for intracellular acidic compartments, and automated confocal microscopy...
To better understand the biology and virulence determinants of two major mycobacterial human pathogens Mycobacterium tuberculosis leprae , their genome sequences have been determined recently. In silico comparisons revealed that among 1439 genes common to both M. 219 code for proteins show no similarity with from other organisms. Therefore, latter ‘core’ could be specific mycobacteria or even intracellular pathogens. obtain more information as whether these really were mycobacteria-specific,...
Despite the validation of direct-acting antivirals for hepatitis C treatment, discovery new compounds with different modes action may still be importance treatment special patient populations. We recently identified a natural molecule, epigallocatechin-3-gallate (EGCG), as an inhibitor virus (HCV) targeting viral particle. The aim this work was to discover higher anti-HCV activity than that EGCG and determine their mode action. Eight molecules structure similarity were selected. HCV JFH1 in...
Antibiotic resistance is one of the biggest threats to human health globally. Alarmingly, multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis have now spread worldwide. Some key antituberculosis antibiotics are prodrugs, for which mechanisms mainly driven by mutations in bacterial enzymatic pathway required their bioactivation. We developed drug-like molecules that activate a cryptic alternative bioactivation ethionamide M. tuberculosis, circumventing classic...
Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC 3.1 μM, is bactericidal active intracellular bacteria. To investigate its mechanism action, we isolated mutants resistant sequenced their genomes. Mutations were found in rv3405c, coding for transcriptional repressor divergently expressed rv3406 gene....
Significance To secure their colonization and survival, pathogens have evolved tactics to undermine host immune responses. Most particularly, Mycobacterium tuberculosis inhibits the activation of macrophages, one whose roles is recognize kill invading microorganisms. Here, we used a library M. mutants infect macrophages uncover molecular mechanisms by which pathogen modulates function these cells. We found that produces cell envelope glycolipids are antagonists macrophage receptor, named...
Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized disruption of gut homeostasis severe acute syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage Syrian hamster model. Our data confirmed model recapitulates some hallmark features human in lungs. further showed SARS-CoV-2 associated mild intestinal inflammation, relative alteration barrier...
Proteins of the 6-kDa early secreted antigenic target (ESAT-6) secretion system-1 Mycobacterium tuberculosis are not only strongly involved in anti-mycobacterial Th1-host immune response but also key players for virulence. In this study, protein engineering together with bioinformatic, immunological, and virulence analyses allowed us to pinpoint regions ESAT-6 molecule that critical its biological activity M. tuberculosis. Mutation Trp-Xaa-Gly motif, conserved a wide variety ESAT-6-like...