Biology subjects

Chevalier, L.

Publications and source records attributed to Chevalier, L..

6 recordsLinked to original sources

bioRxiv2025

Tolerance to the antifungal drug fluconazole is mediated by tuning cytoplasmic fluidity

Treatment failure rates for fungal infections cannot be explained simply by increased rates of drug resistance. Antifungal drug tolerance, the ability of a susceptible isolate to grow in the presence of inhibitory drug concentrations, relies upon a broad set of stress response pathways and can contribute to antifungal drug treatment failures. As the physical properties of the cytoplasm are critical for diverse cellular processes, we investigated whether cytoplasmic mesoscale fluidity is linked to antifungal tolerance, taking advantage of a fluorescent microrheological probe. Here, we show either using fluconazole, a common drug that inhibits ergosterol biosynthesis, or mutants in the ergosterol biosynthesis pathway, that cytoplasmic fluidity decreased and could be reversed upon drug removal. Reducing ribosome concentration decreased drug tolerance and restored cytoplasmic fluidity, highlighting a link between tolerance and cytoplasmic crowding and/or viscosity. However, growth in fluconazole did not increase ribosome concentrations; rather growth in fluconazole increased the number of dormant, hibernating ribosomes, cytoplasmic protein concentration, viscosity and condensate formation. Specifically, growth in fluconazole resulted in a substantial increase in processing bodies (P-bodies), whose presence correlated with azole tolerance. Furthermore, we found a substantial increase in cell-cell heterogeneity in all biophysical, biochemical and molecular outputs analyzed. Together, our results reveal that changes in the physical properties of the cytoplasm occur in response to antifungal drug and suggest that these changes, as well as increased cell-cell heterogeneity, are crucial for survival in fungistatic drugs.

microbiology↗

bioRxiv2025

Quantitative evaluation of dogs as sentinels for Rift Valley fever virus circulation in Madagascar

Sentinel animals may play a key role in surveillance of zoonotic arbovirus circulation, particularly in developing countries with low levels of investment in health. This study aimed to assess the relevance of using dogs as sentinel animals for Rift Valley fever virus (RVFV) surveillance in Madagascar. Serological surveys were conducted on 513 dogs and 135 cattle in the Ifanadiana district. In addition, 486 human dry blood samples available from the same area were used. Serostatus against RVFV was determined using a competitive Enzyme-Linked Immunosorbent Assay (cELISA) for dog and cattle samples, and a Multiplex Bead Assay (MBA) for human samples. Serocatalytic models fitted to age-stratified serological data were developed to estimate the RVF force of infection (FOI) under several hypotheses, ranging from no relationship to proportional FOIs between humans, cattle, and dogs. Antibodies to RVFV were detected in 23 of 513 dogs (4.5%; 95% confidence interval (95% CI): [2.9 - 6.7]), in 86 of 486 humans (17.7%; 95% CI: [14.4 - 21.4]), and in 33 of 135 cattle (24.4%; 95% CI: [17.5 - 32.6]). Based on the deviance information criterion, the best supported model indicated that FOI in humans and cattle was proportional to FOI in dogs. Proportionality parameters were estimated at 2.6 (95% credible interval (95% CrI): [1.4 - 5.1]) for humans and 3.5 (95% CrI: [1.3 - 6.4]) for cattle. Our findings suggest that sampling dogs could be used to identify RVFV circulation in endemic areas, and infer the exposure of humans and cattle in these areas in Madagascar. This original result paves the way for an innovative surveillance method for RVFV in Madagascar and other endemic countries, but also for other arboviruses such as West Nile virus. Author SummaryRift Valley fever (RVF) is a viral zoonosis transmitted by mosquitoes and through contact with the blood, tissues or body fluids of infected animal. The disease has caused at least three major epidemics in Madagascar to date. RVF mainly affects ruminants through abortion and high mortality rate in young animals, and a range of influenza-like to more severe syndromes that can lead to death in some cases in humans. Dogs that interact with humans and are exposed to mosquito bites in the same environment may not develop clinical signs or sufficient viremia to infect vectors, but they could still develop an immune response when exposed to RVF virus (RVFV). This study aimed to assess the relevance of using dogs as sentinel animals for RVFV circulation on the island. Serocatalytic models were developed using serological data to represent and quantify the relationships between the force of infection (FOI) of RVFV exerted on dogs, humans and cattle. We found a proportional relationship between the FOI exerted on dogs and that exerted on humans and cattle. These findings support the relevance of using dogs as sentinel animals for monitoring the circulation of RVFV and arboviruses in general.

pathology↗

bioRxiv2024

Dynamic cytoplasmic fluidity during morphogenesis in a human fungal pathogen

The molecular crowding of the cytoplasm impacts a range of cellular processes. Using a fluorescent microrheological probe (GEMs), we observed a striking decrease in molecular crowding during the yeast to filamentous growth transition in the human fungal pathogen Candida albicans. This decrease in crowding is due to a decrease in ribosome concentration that results in part from an inhibition of ribosome biogenesis, combined with an increase in cytoplasmic volume; leading to a dilution of the major cytoplasmic crowder. Moreover, our results suggest that inhibition of ribosome biogenesis is a trigger for C. albicans morphogenesis.

cell biology↗

bioRxiv2024

Mechanical Strategies Supporting Growth and Size Diversity in Filamentous Fungi

The stereotypical tip growth of filamentous fungi supports their lifestyles and functions. It relies on the polarized remodeling and expansion of a protective elastic cell wall (CW) driven by large cytoplasmic turgor pressure. Remarkably, hyphal filament diameters, and cell elongation rates can vary extensively among different fungi. To date, however, how fungal cell mechanics may be adapted to support these morphological diversities while ensuring surface integrity remains unknown. Here, we combined super-resolution imaging and deflation assays, to measure local CW thickness, elasticity and turgor in a set of fungal species spread on the evolutionary tree that span a large range in cell size and growth speeds. While CW elasticity exhibited dispersed values presumably reflecting differences in CW composition, both thickness and turgor scaled in dose-dependence with cell diameter and growth speeds. Notably, larger cells exhibited thinner lateral CWs, and faster cells thinner apical CWs. Counterintuitively, turgor pressure was also inversely scaled with cell diameter and tip growth speed, challenging the idea that turgor is the primary factor dictating tip elongation rates. We propose that fast growing cells with rapid CW turnover have evolved strategies based on a less turgid cytoplasm and thin walls to safeguard wall integrity and survival.

cell biology↗

bioRxiv2022

Cell Wall Dynamics in a Filamentous Fungus

Hyphal tip growth allows filamentous fungi to colonize space, reproduce or infect. It features remarkable morphogenetic plasticity including unusually fast elongation rates, tip turning, branching or bulging. These shape changes are all driven from the expansion of a protective cell wall (CW) secreted from apical pools of exocytic vesicles. How CW secretion, remodeling and deformation are modulated in concert to support rapid tip growth and morphogenesis while ensuring surface integrity remains poorly understood. We implemented sub-resolution imaging to map the dynamics of CW thickness and secretory vesicles in Aspergillus nidulans. We found that tip growth is associated with balanced rates of CW secretion and expansion, which limit temporal fluctuations in CW thickness, elongation speed and vesicle amount, to less than 10-15%. Affecting this balance through modulations of growth or trafficking yield to near-immediate changes in CW thickness, mechanics and shape. We developed a model with mechanical feedback which accounts for steady states of hyphal growth as well as rapid adaptation of CW mechanics and vesicle recruitment to different perturbations. These data provide unprecedented details on how CW dynamics emerges from material secretion and expansion, to stabilize fungal tip growth as well as promote its morphogenetic plasticity.

cell biology↗

bioRxiv2020

A demogenetic agent based model for the evolution of traits and genome architecture under sexual selection

Sexual selection has long been known to favor the evolution of mating behaviors such as mate preference and competitiveness, and to affect their genetic architecture, for instance by favoring genetic correlation between some traits. Reciprocally, genetic architecture can affect the expression and the evolvability of traits and mating behaviors. But sexual selection is highly context-dependent, making interactions between individuals a central process in evolution, governing the transmission of genotypes to the next generation. This loop between the genetic structure conditioning the expression and evolution of traits and behaviour, and the feedback of this phenotypic evolution on the architecture of the genome in the dynamic context of sexual selection, has yet to be thoroughly investigated. We argue that demogenetic agent-based models (DG-ABM) are especially suited to tackle such a challenge because they allow explicit modelling of both the genetic architecture of traits and the behavioural interactions in a dynamic population context. We here present a DG-ABM able to simultaneously track individual variation in traits (such as gametic investment, preference, competitiveness), fitness and genetic architecture throughout evolution. Using two simulation experiments, we compare various mating systems and show that behavioral interactions during mating triggered some complex feedback in our model, between fitness, population demography, and genetic architecture, placing interactions between individuals at the core of evolution through sexual selection. DG-ABMs can, therefore, relate to theoretical patterns expected at the population level from simpler analytical models in evolutionary biology, and at the same time provide a more comprehensive framework regarding individual trait and behaviour variation, that is usually envisioned separately from genome architecture in behavioural ecology.

evolutionary biology↗