A5084766997- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Metabolomics and Mass Spectrometry Studies
- Cancer, Lipids, and Metabolism
- Bacterial Identification and Susceptibility Testing
- Infectious Diseases and Tuberculosis
- Spectroscopy Techniques in Biomedical and Chemical Research
- Mass Spectrometry Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Antibiotics Pharmacokinetics and Efficacy
- Immune Response and Inflammation
- Diagnosis and treatment of tuberculosis
- Antifungal resistance and susceptibility
- Bacteriophages and microbial interactions
- Immune cells in cancer
- Spectroscopy and Chemometric Analyses
- interferon and immune responses
- Autophagy in Disease and Therapy
- Bacillus and Francisella bacterial research
- Target Tracking and Data Fusion in Sensor Networks
- Bacterial Infections and Vaccines
- Computability, Logic, AI Algorithms
- Pneumonia and Respiratory Infections
- Peroxisome Proliferator-Activated Receptors
Centre National de la Recherche Scientifique
2017-2025
Université de Bordeaux
2020-2025
Institut Polytechnique de Bordeaux
2020-2025
Institut de Pharmacologie et de Biologie Structurale
2013-2024
Université Toulouse III - Paul Sabatier
2017-2024
Université de Toulouse
2013-2024
Chimie et Biologie des Membranes et des Nanoobjects
2020-2022
Institut Européen de Chimie et Biologie
2021-2022
Rutgers, The State University of New Jersey
2017-2021
Centre de Recherche Cardio-Thoracique de Bordeaux
2021
ABSTRACT Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence, and drug tolerance are among factors driving long duration. Assays measure situ susceptibility Mycobacterium tuberculosis bacteria pulmonary lesions needed if we discover new fast-acting regimens address global TB threat. Here take a first step toward this goal describe an ex vivo assay developed cidal activity anti-TB drugs...
The length and complexity of tuberculosis (TB) therapy, as well the propensity Mycobacterium to develop drug resistance, are major barriers global TB control efforts. M. is known have ability enter into a drug-tolerant state, which may explain many these impediments treatment. We identified mechanism genetically encoded but rapidly reversible tolerance in caused by transient frameshift mutations homopolymeric tract (HT) 7 cytosines (7C) glpK gene. Inactivating associated with 7C HT produce...
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...
Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these form during a infectious disease such as tuberculosis is unknown. Here we report that, unlike cholesterol-laden of tuberculous lung lesions accumulate triglycerides. Consequently, varies underlying disease. In vitro mechanistic studies showed triglyceride...
Intra-abdominal candidiasis (IAC) is a prominent invasive fungal infection associated with high mortality. Prompt antifungal therapy and source control are crucial for successful treatment. Echinocandin drugs first-line agents; however, their clinical effectiveness highly variable, known potential breakthrough resistance, little about drug exposure at the site of infection. Using matrix-assisted desorption ionization mass spectrometry imaging technology, we investigated spatial quantitative...
Clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts drug's rather modest potency lack activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile suggests drug may be limited clinical value. Here, we hypothesized this apparent contradiction explained by favorable penetration into TB lesions. First, utilized novel in vitro lesion pharmacokinetic...
MALDI mass-spectrometry imaging (MALDI-MSI) is a technique capable of the label-free identification and visualization analytes in tissue sections. We have previously applied MALDI-MSI to study spatial distribution tuberculosis (TB) drugs necrotic lung granulomas characteristic pulmonary TB disease, revealing heterogeneous often suboptimal drug distributions. To investigate impact differential distributions at sites infection, we sought image mycobacterial biomarkers coregister bacteria...
Caseous necrosis is a hallmark of tuberculosis (TB) pathology and creates niche for drug-tolerant persisters within the host. Cavitary TB high bacterial burden in caseum require longer treatment duration. An vitro model that recapitulates major features Mycobacterium (Mtb) would accelerate identification compounds with treatment-shortening potential. We have developed surrogate consisting lysed denatured foamy macrophages. Upon inoculation Mtb from replicating cultures, pathogen adapts to...
Understanding the distribution patterns of antibiotics at site infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made various immune cell types, some which harbor persistent forms pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining quantitative image analysis in rabbits active TB, we have mapped a fluoroquinolone resolution, identified immune-pathological factors...
Fluoroquinolones represent the pillar of multidrug-resistant tuberculosis (MDR-TB) treatment, with moxifloxacin, levofloxacin, or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials “universal” drug regimens, aiming treat drug-susceptible and drug-resistant TB, have included a fluoroquinolone.
Background Bronchial smooth muscle (BSM) remodelling in asthma is related to an increased mitochondrial biogenesis and enhanced BSM cell proliferation asthma. Since mitochondria produce the highest levels of cellular energy fatty acid β-oxidation most powerful way ATP, we hypothesised that, asthmatic cells, energetic metabolism shifted towards acids. Objectives We aimed characterise both vitro ex vivo identify a novel target for reducing proliferation. Methods 21 31 non-asthmatic patients...
Tuberculosis is still a leading cause of morbidity and mortality worldwide. Improvements to existing drug regimens the development novel therapeutics are urgently required. The ability dosed TB drugs reach sterilize bacteria within poorly-vascularized necrotic regions (caseum) pulmonary granulomas crucial for successful therapeutic intervention. Effective must therefore contain with favorable caseum penetration properties. Current LC/MS methods quantifying levels in biological tissues have...
In the 1970s, inclusion of pyrazinamide (PZA) in drug regimen tuberculosis (TB) patients for first 2 mo achieved a drastic reduction therapy duration. Until now, however, mechanisms underlying PZA’s unique contribution to efficacy have remained controversial, and animal data vary across species. To understand how PZA kills bacterial populations present critical lung lesion compartments, we characterized rabbit model active TB, showing striking similarities types fates nonhuman primate models...
Abstract Overweight and obesity have been shown to significantly affect brain structures size. Obesity has associated with cerebral atrophy, alteration of functions, including cognitive impairement, psychiatric diseases such as depression. Given the importance lipids in structure brain, here, by using 47 mice fed a high fat diet (HFD) 60% calories from (40% saturated fatty acids) 20% carbohydrates age-matched control animals on normal chow diet, we examined effects HFD diet-induced lipidome....
Abstract Background Cavitary tuberculosis is difficult to cure and constitutes a site of relapse. Bedaquiline has been wonder drug in the treatment multidrug resistanttuberculosis, but emergence resistance threatens sustainability its success. We designed site-of-disease pharmacokinetic studies preclinical species spatially resolve penetration bedaquiline, two next generation diarylquinolines TBAJ587 TBAJ876, necrotic center (caseum) cavities. Methods Rabbits with cavitary received study...
Abstract In this work, we introduce a multimodal imaging workflow that integrates Matrix-assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) combined with Immunofluorescence (IF) microscopy to enhance in tissue spatial single-cell metabolomics. The allows correlate cell populations associated small molecule distributions by conducting on the same section MSI before IF staining, addressing integrity challenges and joint image analysis. To process data guidance, propose...
Innate immune recognition is the first line of host defense against invading microorganisms. It a based on detection, by pattern receptors (PRRs), invariant molecular signatures that are unique to TLR2 PRR plays major role in detection Gram-positive bacteria recognizing cell envelope lipid-linked polymers, also called macroamphiphiles, such as lipoproteins, lipoteichoic acids and mycobacterial lipoglycans. These microbe-associated patterns (MAMPs) display structure lipid anchor, being either...
Mycobacterium abscessus is a prevalent pathogenic mycobacterium in cystic fibrosis (CF) patients and one of the most highly drug resistant mycobacterial species to antimicrobial agents. It possesses property transition from smooth (S) rough (R) morphotype, thereby influencing host innate immune response. This S R morphotype takes place with an exacerbation disease persistence M. abscessus. We have previously shown that Toll-like receptor 2 (TLR2)-mediated inflammatory response, following...
Abstract Cancer-associated adipocytes (CAAs) have emerged as pivotal players in various cancers, particularly such breast cancer, significantly influencing their progression and therapy resistance. Understanding the adipocytes/cancer cells crosstalk is crucial for effective treatment strategies. Raman spectroscopy, a label-free optical technique, offers potential characterizing biological samples by providing chemical-specific information. In this study, we used spectroscopy Trajectory...
Tuberculosis is still a leading cause of morbidity and mortality worldwide. Improvements to existing drug regimens the development novel therapeutics are urgently required. The ability dosed TB drugs reach sterilize bacteria within poorly-vascularized necrotic regions (caseum) pulmonary granulomas crucial for successful therapeutic intervention. Effective must therefore contain with favorable caseum penetration properties. Current LC/MS methods quantifying levels in biological tissues have...