A5016577934- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Antibiotic Resistance in Bacteria
- Immune Cell Function and Interaction
- Infectious Diseases and Tuberculosis
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Escherichia coli research studies
- Viral Infections and Vectors
- CAR-T cell therapy research
- Vector-borne infectious diseases
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Carbohydrate Chemistry and Synthesis
- interferon and immune responses
- Cancer Research and Treatments
- Diagnosis and treatment of tuberculosis
- Bacterial Genetics and Biotechnology
- Dermatological diseases and infestations
Institut Pasteur
2016-2024
Université Paris Cité
2024
Amsterdam University Medical Centers
2018-2023
University of Amsterdam
2018-2022
Vrije Universiteit Amsterdam
2019-2022
Centre National de la Recherche Scientifique
2018-2021
Amsterdam UMC Location Vrije Universiteit Amsterdam
2015-2018
Amsterdam UMC Location University of Amsterdam
2018
Department of Genomes & Genetics
2018
Biology of Infection
2016
Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the multiple substrates. However, role ESX-5 substrates growth and/or virulence largely unknown. In this study, we show that esx-5 essential both Mycobacterium marinum bovis. Remarkably, essentiality can be rescued by increasing permeability outer membrane, either altering its...
Type VII secretion (T7S) systems of mycobacteria secrete substrates over the unusual diderm cell envelope. Furthermore, T7S gene clusters are present throughout phylum Actinobacteria, and functional T7S-like have been identified in Firmicutes. Most can be divided into two families: Esx proteins, which found both Firmicutes PE PPE more mycobacterium-specific. Members families shown to secreted as folded heterodimers, suggesting that this is a conserved feature substrates. knowledge mechanism...
Mycobacteria produce a capsule layer, which consists of glycan-like polysaccharides and number specific proteins. In this study, we show that, in slow-growing mycobacteria, the type VII secretion system ESX-5 plays major role integrity stability capsule. We have identified PPE10 as substrate responsible for effect. Mutants esx-5 ppe10 both impaired well reduced surface hydrophobicity. Electron microscopy, immunoblot flow cytometry analyses demonstrated amounts localized proteins glycolipids,...
Mycobacterium africanum consists of Lineages L5 and L6 the tuberculosis complex (MTBC) causes human in specific regions Western Africa, but is generally not transmitted other parts world. Since M. evolutionarily closely placed between globally dispersed animal-adapted MTBC-members, these lineages provide valuable insight into evolution. Here, we have collected 15 strains isolated France over 4 decades. Illumina sequencing phylogenomic analysis revealed a previously underappreciated diversity...
Tuberculosis is the deadliest infectious disease worldwide. Although BCG vaccine widely used, it does not efficiently protect against pulmonary tuberculosis and an improved therefore urgently needed. Mycobacterium uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence host immune responses. We recently reported that of T7S substrates belonging mycobacteria-specific Pro-Glu (PE) Pro-Pro-Glu (PPE) PGRS (polymorphic GC-rich sequences) MPTR (major...
The pathogenic potential of Mycobacterium tuberculosis largely depends on ESX secretion systems exporting members the multigenic Esx, Esp, and PE/PPE protein families. To study regulation patterns these proteins while circumventing immune cross-reactions due to their extensive sequence homologies, we developed an approach that relies recognition MHC class II epitopes by highly discriminative T cell receptors (TCRs) a panel hybridomas. latter were engineered so each expresses unique...
Mycobacterium microti is an animal-adapted member of the tuberculosis complex (MTBC), which was originally isolated from voles, but has more recently also been other selected mammalian hosts, including occasionally humans. Here, we have generated and analysed complete genome sequences five representative vole clinical M. isolates using PacBio- Illumina-based technologies, tested their virulence vaccine potential in SCID (severe combined immune deficient) mouse and/or guinea pig infection...
T-cell antigen receptor (TCR) interaction with cognate peptide:MHC complexes trigger clustering of TCR:CD3 and signal transduction. Triggered are rapidly internalized degraded in a process called ligand-induced TCR downregulation. Classic studies immortalized lines have revealed major role for the Src family kinase Lck However, to what extent similar mechanism operates primary human T cells remains unclear.Here, we developed an anti-CD3-mediated downregulation assay, which gene expression...
Mycobacterium bovis Bacille Calmette-Guérin (BCG) is not only used as a vaccine against tuberculosis but also protects leprosy and part of bladder cancer treatment to induce protective immune response. However, protection by BCG vaccination optimal. To improve efficacy, recombinant expressing heterologous antigens has been put forward elicit antigen-specific cellular humoral responses. Cell surface localized or secreted better responses than their cytosolic counterparts. Optimizing secretion...
Background Interferon (IFN)-β induction via activation of the stimulator interferon genes (STING) pathway has shown promising results in tumor models. STING is activated by cyclic dinucleotides such as GMP–AMP with phosphodiester linkages 2′–5′ and 3′–5′ (cGAMPs), that are produced synthetase (cGAS). However, delivery agonists to site a challenge. Bacterial vaccine strains have ability specifically colonize hypoxic tissues could therefore be modified overcome this Combining high...
Abstract Reconstructing the evolutionary origins of Mycobacterium tuberculosis , causative agent human tuberculosis, has helped identify bacterial factors that have led to tubercle bacillus becoming such a formidable pathogen. Here we report discovery and detailed characterization an exceedingly slow growing mycobacterium is closely related M. for which proposed species name spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from marine sponge, taken waters Great Barrier...
Reconstructing the evolutionary origins of Mycobacterium tuberculosis, causative agent human has helped identify bacterial factors that have led to tubercle bacillus becoming such a formidable pathogen. Here we report discovery and detailed characterization an exceedingly slow growing mycobacterium is closely related M. tuberculosis for which proposed species name spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from marine sponge, taken waters Great Barrier Reef in...
Abstract Tuberculosis is the deadliest infectious disease worldwide. Although BCG vaccine widely used, it does not efficiently protect against pulmonary tuberculosis and an improved therefore urgently needed. Mycobacterium uses different ESX/Type VII secretion (T7S) systems to transport proteins important for virulence host immune responses. We recently reported that of T7S substrates belonging mycobacteria-specific Pro-Glu (PE) Pro-Pro-Glu (PPE) PGRS (polymorphic GC-rich sequences) MPTR...
ABSTRACT Genetic manipulation of primary lymphocytes is crucial for both clinical purposes and fundamental research. Despite their broad use, we encountered a paucity data on systematic comparison optimization retroviral vectors, the workhorses genetic modification lymphocytes. Here, report construction validation versatile range expression vectors. These vectors can be used knockdown or overexpression genes interest in human murine lymphocytes, combination with wide choice selection...
Abstract Genetic manipulation of primary lymphocytes is crucial for both clinical purposes and fundamental research. Despite their broad use, we encountered a paucity data on systematic comparison optimization retroviral vectors, the workhorses genetic modification lymphocytes. Here, report construction validation versatile range expression vectors. These vectors can be used knockdown or overexpression genes interest in human murine lymphocytes, combination with wide choice selection...