Biology subjects

Guitard, J.

Publications and source records attributed to Guitard, J..

5 recordsLinked to original sources

bioRxiv2026

Integrin beta 1 and mannose receptor 2 are involved in the antifungal activity of bronchial epithelial cells through Aspergillus fumigatus lectin FleA interactions

Aspergillus fumigatus is a world-wide saprophyte filamentous fungus which released conidia, its infectious morphotype, in the atmosphere. These conidia are inhaled daily by humans and can colonize the respiratory tract, where they may develop into hyphae, the invasive morphotype. We previously showed that bronchial epithelial cells (BECs) restrict A. fumigatus virulence by inhibiting conidial germination and filament formation through a process requiring PI3K signaling and the conidial fucose-specific lectin FleA. In the present study, we are looking to identify host factors and cellular partners involved in the BEC antifungal response and to define the molecular interactions underpinning FleA recognition. For this, we analyzed transcriptome of BECs infected with A. fumigatus in the presence or absence of the PI3K inhibitor LY294002. Functional involvement of candidate genes was assessed by siRNA knockdown and readouts of fungal filamentation (microscopic scoring and galactomannan release). FleA-interacting host proteins were identified by biotin-FleA affinity co-precipitation coupled to Tandem mass spectrometry, and validated by surface plasmon resonance and biolayer interferometry. The spatiotemporal dynamics of FleA and candidate partners were analyzed by confocal microscopy and proximity ligation assay We demonstrated that BEC antifungal activity involves at least two complementary pathways: a PI3K/laminin-332 axis promoting conidial adhesion, and a FleA-dependent pathway engaging ITGB1 and MRC2 consistent with lectin uptake and trafficking toward LAMP1-positive compartments. These findings nominate FleA-host receptor interactions as attractive targets for anti-adhesive strategies against A. fumigatus. Author summaryFungal pathogens are an increasing threat to public health, as they are becoming more common and harder to treat due to rising drug resistance. Among them, Aspergillus fumigatus has been classified as a critical pathogen by the World Health Organization (WHO). This filamentous fungus delivers spores in the air daily, which are constantly inhaled by humans. In people with weakened immunity, these spores can cause a range of lung diseases known as aspergillosis, with severity ranging from mild to life-threatening. Lung epithelial cells are the first cells of the respiratory tract to encounter inhaled spores. In a previous study, we showed that bronchial cells can prevent spore from developing into filaments, the invasive form of A. fumigatus that is responsible for tissue damage. This protective effect depends of on the recognition of a fungal protein called FleA. In the present study, we identified host cell proteins that bind to FleA and transport it into intracellular compartments. Our findings suggest that these proteins help bronchial epithelial cells to internalize fungal spores, thereby blocking their transformation into the invasive filamentous form.

cell biology↗

bioRxiv2025

Past environments modulate response to fluctuating temperatures in a marine fish species

The rise in ocean temperatures predicted due to the global warming will impact the survival and structure of various marine organisms, in particular ectothermic organisms. Phenotypic plasticity enables species to cope with environmental changes, providing a vital buffer for evolutionary changes. Yet, the dynamics and the molecular mechanisms underpinning these plastic responses remain largely unexplored. Here, we assessed the impact of acclimation environment on organisms capacity for thermal plasticity. We conducted a genome-wide transcriptomic analysis on the Acadian redfish, S. fasciatus, exposed to four temperatures (2.5, 5.0, 7.5 and 10.0 ) over a long-term period (up to 10 months) followed by an acute temperature change (24 hours), simulating natural fluctuation condition the species could encounter. Our results showed a dynamic transcriptional response to temperature involving various genes functions. The rapid response to temperature shifts, coupled with the sustained expression of specific genes over an extended period highlighted the species capacity for plastic response to temperature changes. We also detected a significant effect of the interaction between the long and short terms temperature exposure on gene expression, highlighting the influence of the past environment on response to acute temperature changes. Specifically, fish acclimated to higher temperatures demonstrated an increased stress-related response to environmental fluctuations, as evidenced by both the shape of their reaction norms and the implication of stress-related gene functions. This result suggests that temperature conditions predicted for the near future in the Northwest Atlantic will trigger less adaptive plasticity to environmental fluctuations, highlighting the species vulnerability to ocean warming.

ecology↗

bioRxiv2025

The epigenomic landscape of bronchial epithelial cells reveals the establishment of trained immunity

BackgroundInnate immune memory, also called trained immunity, refers to the ability of innate immune cells to gain memory characteristics after transient stimulation, resulting in a nonspecific modified inflammatory response upon secondary remote challenge. Bronchial epithelial cells (BECs) participate in innate immune defence and are the first cells of the lower respiratory tract to encounter inhaled pathogens. We recently showed that BECs are capable of innate immune memory after preexposure to Pseudomonas aeruginosa flagellin through epigenetic mechanisms. In the present study, we investigated such mechanisms through the modification of chromatin architecture induced by flagellin preexposure that results in subsequent changes of gene expression. ResultsBy conducting an unsupervised approach to jointly analyse chromatin accessibility and gene expression, we mapped the remodelling of the epigenomic and transcriptomic profiles during the establishment of BECs memory. We identified a Memory regulatory profile induced by flagellin exposure. It includes clusters of upregulated genes related to inflammation that are linked to a sustainable gain in chromatin accessibility and with an increased activity of specific factors (TFs) whose binding may drive this process. ConclusionsIn summary, we demonstrated that flagellin exposure induced changes in chromatin condensation in BECs, which sustains the reprogramming of transcriptional patterns

genetics↗

bioRxiv2024

New insights into the echinocandin resistance in Candida spp. in the clinical setting

Despite a huge consumption of echinocandins, the emergence of resistance in Candida spp has remained overall limited. Here, we depicted the epidemiology of Candida spp in our center face to the echinocandins consumption. We postulate new hypotheses that may explain the shaping of candines resistance in the clinical setting. Epidemiology of Candida infections and echinocandin consumption were evaluated in our center over 12 years (2006-2018). Glucan synthase genes (fks1, fks2) were sequenced. The in vitro fitness was assessed for couple of isogenic strains, of which one was resistant. Finally, the modelling of Candida FKS proteins was realized. Despite a three-fold increase in echinocandin consumption, no significant emergence of resistance was observed. In Candida albicans, fks1 mutations affect the three-dimensional conformation of the glucan synthase, which may result in altered export of the glucan chain, which could explain the observed reduced fitness. In contrast, cross-complementation between FKS1 and FKS2 in Nakaseomyces glabratus might circumvent the negative impact on fitness. ConclusionsOur results support the fact that N. glabratus is more prone to the spread of echinocandin-resistant strains. The link between mutations in the glucan synthase and fitness of Candida strains might explain the difference in the species-specific emergence of echinocandins-resistant strains.

microbiology↗

bioRxiv2023

Molecular epidemiology of Candida africana isolates collected from vagina swabs in French Guiana.

Candida africana corresponds to the clade 13 of Candia albicans. It has been mostly involved in vulvovaginal candidiasis worldwide but few data exist in South America. The aim of our study was to investigate the prevalence of C. africana in women living in French Guiana. For this, we first set up a fluorescent-intercalating-dye-real time PCR targeting the hyphal wall protein 1 gene. The test was applied to 212 C. albicans isolates collected from May to August 2019 from vaginal swabs, allowing the identification of 6 women harboring C. africana (8 isolates). No demographics or clinical-specific features could be demonstrated. Genetic diversity of those isolates was analyzed through multilocus sequence typing and showed that diploid sequence type 182 was predominant (n=6) and allowed the report of a new diploid sequence type.

microbiology↗