A5089641764- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Infectious Diseases and Mycology
- Antibiotic Resistance in Bacteria
- Aquaculture disease management and microbiota
- interferon and immune responses
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacteriophages and microbial interactions
- Cystic Fibrosis Research Advances
- Gut microbiota and health
- Infectious Diseases and Tuberculosis
- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Immunodeficiency and Autoimmune Disorders
- Herpesvirus Infections and Treatments
- Actinomycetales infections and treatment
- Antimicrobial Peptides and Activities
- Immune cells in cancer
- Vector-Borne Animal Diseases
- Advanced Biosensing Techniques and Applications
- Diphtheria, Corynebacterium, and Tetanus
- Advanced biosensing and bioanalysis techniques
- Vibrio bacteria research studies
- Acoustic Wave Resonator Technologies
Université Paris-Saclay
2018-2025
Inserm
2016-2025
Université de Versailles Saint-Quentin-en-Yvelines
2014-2025
Infection et inflammation
2015-2024
Hôpital Ambroise-Paré
2019
Hôpital Raymond-Poincaré
2019
Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail
2010-2015
Institut thématique Immunologie, inflammation, infectiologie et microbiologie
2015
University of Verona
2007-2012
Institut Universitaire de Recherche Clinique
2012
Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for wide spectrum of clinical manifestations ranging from pulmonary to skin soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms amoebae macrophages, ability that has not been observed in other RGM. M. abscessus up-regulate several virulence factors during transient infection amoebae, thereby becoming more virulent subsequent...
ABSTRACT Mycobacterium abscessus pulmonary infections are treated with a macrolide (clarithromycin or azithromycin), an aminoglycoside (amikacin), and β-lactam (cefoxitin imipenem). The triple combination is used without any β-lactamase inhibitor, even though M . produces the broad-spectrum Bla Mab We determine whether inhibition of by avibactam improves activity imipenem against M. bactericidal drug combinations was assayed in broth human macrophages. vivo efficacy drugs tested monitoring...
Abstract Neutrophils, historically known for their involvement in acute inflammation, are also targets infection by many different DNA and RNA viruses. However, the mechanisms which they recognize respond to viral components poorly understood. Polyinosinic:polycytidylic acid (poly(I:C)) is a synthetic mimetic of dsRNA that interact either with endosomal TLR3 (not expressed human neutrophils) or cytoplasmic helicases such as melanoma differentiation-associated gene 5 (MDA5) retinoic...
Abstract LPS activates both MyD88-dependent and -independent signaling via TLR4, but the extent to which each cascade is operative in different cell types remains unclear. This prompted us revisit intriguing issue of CXCL10 production, we previously showed be inducible neutrophils stimulated with IFN-γ not either stimulus alone, contrary other myeloid cells. We now report that MyD88-independent pathway activated by LPS. Indeed, microarray real-time PCR experiments neither IFNβ nor...
Mycobacterium abscessus is responsible for a wide spectrum of clinical syndromes and one the most intrinsically drug-resistant mycobacterial species. Recent evaluation in vivo therapeutic efficacy few potentially active antibiotics against M. was essentially performed using immunocompromised mice. Herein, we assessed feasibility sensitivity fluorescence imaging monitoring activity drugs acute infection zebrafish embryos. A protocol developed where clarithromycin imipenem were directly added...
Significance Mycobacterium abscessus is currently the most frequently isolated rapid-growing mycobacterium in human pathology and responsible for devastating pulmonary infections cystic fibrosis patients. It commutes from a nonvirulent smooth to virulent rough morphotype. The latter produces characteristic serpentine cords that often associate with severe infections, but molecular basis contribution of cording physiopathology infection remain obscure. Herein, we characterized dehydratase...
Free-living amoebae are thought to represent an environmental niche in which amoeba-resistant bacteria may evolve towards pathogenicity. To get more insights into factors playing a role for adaptation intracellular life, we characterized the transcriptomic activities of emerging pathogen Mycobacterium abscessus amoeba and murine macrophages (Mϕ) compared them with intra-amoebal transcriptome closely related, but less pathogenic chelonae. Data on up-regulated genes point proteins that allow...
Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium involved in pulmonary and cutaneo-mucous infections worldwide, to which cystic fibrosis patients are exquisitely susceptible. The analysis of the genome sequence M. showed that this bacterium endowed with metabolic pathways typically found environmental microorganisms come into contact soil, plants, aquatic environments, where free-living amoebae frequently present. also contains several genes characteristically only...
Significance One major defense mechanism of mycobacteria relies mainly on the synthesis and transport specialized lipids, processes that reside in cell wall. Among transporters, Mycobacterial membrane protein Large (MmpL) plays an essential role. We describe role MmpL8 (MmpL8 MAB ) survival Mycobacterium abscessus within eukaryotic hosts. show its absence slows contact between M. host cytosol, element resistance to bactericidal mechanisms. The leads reduced production a previously unknown...
Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations antibiotics, such as bedaquiline and imipenem, although in vitro data questioned this combination. We report that efficacy bedaquiline-imipenem combination treatment relies essentially on activity a C3HeB/FeJ mice model infection with rough variant M. . The addition imipenem contributed clearing spleen.
Twelve new Cyclophostin and Cyclipostins analogues (CyC19-30) were synthesized, thus extending our series to 38 CyCs. Their antibacterial activities evaluated against four pathogenic mycobacteria (Mycobacterium abscessus, Mycobacterium marinum, bovis BCG, tuberculosis) two Gram negative bacteria. The CyCs displayed very low toxicity toward host cells only active mycobacteria. Importantly, several extracellular M. abscessus (CyC17/CyC18β/CyC25/CyC26) or intramacrophage residing...
Abstract Type VII secretion systems participate in protein export, virulence, conjugation, and metabolic regulation. Five subtypes (ESX-1 to ESX-5) exist, each with specific roles well-characterized profiles various mycobacterial species. Mycobacterium abscessus , encodes only ESX-3 ESX-4. Here, single double M. mutants lacking the main ATPases EccC3 EccC4 were used define ESX-4 contributions substrate virulence. Our results demonstrate that EsxG/H depends entirely on ESX-3, whereas both...
Mycobacterium abscessus is the most frequent of rapidly growing mycobacteria responsible for lung infections in patients suffering from cystic fibrosis and COPD. Imipenem currently recommended treatment these spite β-lactamase production. Since targets β-lactams include transpeptidases both l,d d,d specificities, we tested, vitro, intracellularly vivo, a combination two active on enzymes, amoxicillin imipenem, alone or with inhibitor relebactam. Drug combinations were evaluated against M....
Abstract Pathogenic mycobacteria produce a wide array of lipids which participate in host cell interactions and virulence. While some these are conserved across all mycobacteria, others, like glycopeptidolipids (GPL), restricted to few species. Mycobacterium abscessus , an emerging rapid-growing pathogen, transitions from smooth virulent rough variant upon the loss surface GPL. Here, we discovered that M. phylogenetically-close species harbor second GPL-related locus, comprising two adjacent...
Upon LPS binding, TLR4 activates a MyD88-dependent pathway leading to the transcriptional activation of proinflammatory genes, as well MyD88-independent/TRIF-dependent pathway, responsible for induction IFN-β. Previous findings delineated that human neutrophils are unable induce transcription IFN-β in response stimulation. Because do not express protein kinase C ε, molecule recently reported essential initiating we optimized an electroporation method transfect PKCε into with very high...
Mycobacterium abscessus is an emerging pathogenic mycobacterium involved in pulmonary and mucocutaneous infections, presenting a serious threat for patients with cystic fibrosis (CF). The lack of efficient treatment regimen the emergence multidrug resistance clinical isolates require development new therapeutic strategies against this pathogen. Reverse genetics has revealed genes that are present M. but absent from saprophytic mycobacteria potentially pathogenicity. Among them, MAB_3593...
Mycobacterium abscessus, a pathogen responsible for severe lung infections in cystic fibrosis patients, exhibits either smooth (S) or rough (R) morphotypes. The S-to-R transition correlates with inhibition of the synthesis and/or transport glycopeptidolipids (GPLs) and is associated an increase pathogenicity animal human hosts. Lsr2 small nucleoid-associated protein highly conserved mycobacteria, including M. functional homologue heat-stable nucleoid-structuring (H-NS). It essential...
ESX type VII secretion systems are complex machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake conjugation. We previously reported of ESX-4 modulating Mycobacterium abscessus intracellular survival. The loss EccB4 was associated with limited two effector proteins belonging to WXG-100 family, EsxU EsxT, encoded by esx-4 locus. This prompted us investigate function M . EsxT vitro vivo Herein, we show that substrates form a stable...
Abstract Non‐tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus , are increasing globally. Due to their intrinsic drug resistance, M. pulmonary infections often difficult cure using standard chemotherapy. We previously demonstrated that a piperidinol derivative, named PIPD1, is an efficient molecule both against and tuberculosis the agent of tuberculosis, targeting mycolic acid transporter MmpL3. These results prompted us design synthesize series...
Abstract Free-living amoebae might represent an evolutionary niche. In order to get more insights into the potential amoebal training ground for Mycobacterium abscessus , we characterized its full transcriptome in amoeba (Ac) and macrophages (Mφ), as well chelonae intra-Ac comparison. Up-regulated genes Ac allowed M. resist environmental stress induce defense mechanisms, showing switch from carbohydrate carbon sources fatty acid metabolism. Eleven implicated adaptation intracellular stress,...