Biology subjects

Bernard, O.

Publications and source records attributed to Bernard, O..

4 recordsLinked to original sources

bioRxiv2025

Furin Inhibition Protects Against Acute Lung Injury in a Mouse Model of Pseudomonas Aeruginosa Infection

Pseudomonas aeruginosa (PA) is responsible for significant morbidity and mortality particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF) as well as hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The rise of antibiotic-resistant PA strains necessitates alternative treatment strategies. Among the different toxins secreted by PA, Exotoxin-A (Exo-A) becomes cytotoxic when cleaved by furin. This study investigates the therapeutic potential of furin inhibitor BOS-318 in mitigating acute lung injury induced by Exo-A and PA infection. Furin inhibition significantly improved survival rates and reduced lung injury in mouse pneumonia models using Exo-A and PA103. Additionally, BOS-318 accelerated bacterial clearance in vivo, and increased phagocytosis by alveolar macrophages. Bulk RNA-seq immune profiling revealed modulation of the natural killer (NK) cell signaling pathway possibly due to a decrease in NK recruitment, suggesting a role of furin in shaping the immune response. Overall, our findings demonstrate that furin inhibition protects against PA-induced acute lung injury and hastens bacterial clearance. These results are the first to characterize furin inhibition in animal models and supports its potential use as an adjunctive therapeutic strategy for treating PA infections.

immunology↗

bioRxiv2022

A universal dynamical metabolic model representing mixotrophic growth of Chlorella sp.

An emerging idea is to couple wastewater treatment and biofuel production using microalgae to achieve higher productivities and lower costs. This paper proposes a metabolic modelling of Chlorella sp. growing on wastes in mixotrophic conditions, accounting also for the possible inhibitory substrates. A metabolic model considering several possible carbon substrates was developed and run. The addition of several organic carbon substrates such as acetate, butyrate or glucose were tested, along with glycerol, a more realistic substrate from an economical point of view. The metabolic model was built using DRUM framework and consists of 188 reactions and 176 metabolites. After a calibration phase, the model was successfully challenged with data from 122 experiments collected from scientific literature in autotrophic, heterotrophic and mixotrophic conditions. The optimal feeding strategy estimated with the model reduces the time to consume the volatile fatty acids from 16 days to 2 days. The high prediction capability of this model opens new routes for enhancing design and operation in waste valorisation using microalgae. Author SummaryWaste valorisation is one of the current envisaged strategies to make renewable processes more economically advantageous. For example, wastewater treatment can be used to produce biohydrogen from bacteria, through a process called dark fermentation, and to cultivate microalgae for biofuel production. Dark fermentation has, as by-products, organic acids that have inhibitory effects on the growth of microalgae, increasing the time to completely treat the waste. Advances in metabolic knowledge and techniques allow for the deployment of new strategies to improve the efficiency of bioprocesses. In this work, we validate a mathematical model of the metabolism of the microalgae genus Chlorella using the DRUM framework for 122 experiments from the scientific literature. This model enables us to apply control and optimisation techniques to provide a strategy to treat wastes coming from dark fermentation processes, overcoming the inhibition of some organic acids. The strategy is able to reduce the time to treat the waste from 16 days to only 2 days. The high prediction capability of this model opens new routes for enhancing design and operation in waste valorisation using microalgae.

systems biology↗

bioRxiv2020

A thermal trade-off between viral production and degradation drives phytoplankton-virus population dynamics

Marine viruses interact with their microbial hosts in dynamic environments shaped by variations in abiotic factors, including temperature. However, the impacts of temperature on viral infection of phytoplankton are not well understood. Here we coupled mathematical modeling with experimental datasets to explore the effect of temperature on three Micromonas-prasinovirus pairs. Our model shows the negative consequences of high temperatures on infection and suggests a temperature-dependent threshold between viral production and degradation. Modeling long-term dynamics in environments with different average temperatures revealed the potential for long-term host-virus coexistence, epidemic free, or habitat loss states. Hence, we generalized our model to global sea surface temperature of present and future seas and show that climate change may influence virus-host dynamics differently depending on the virus-host pair. Our study suggests that temperature-dependent changes in the infectivity of virus particles may lead to shifts in virus-host habitats in warmer oceans, analogous to projected changes in the habitats of macro- and micro-organisms.

ecology↗

bioRxiv2018

Inhibition of platelet function by targeting the platelet cytoskeleton via the LIMK-signaling pathway.

Actin is highly abundant in platelets, and platelet function is dependent on actin structures. Actin filaments are dynamic structures involved in many cellular processes including platelet shape changes and adhesion. The actin cytoskeleton is tightly regulated by actin-binding proteins, which include the members of the actin depolymerising factor (ADF)/cofilin family. LIM kinase (LIMK) and slingshot phosphatase (SSH-1L) regulate actin dynamics by controlling the binding affinity of ADF/cofilin towards actin. We hypothesised that inhibition of LIMK activity may prevent the changes in platelet shape during their activation and therefore their function by controlling the dynamics of Factin. Therefore, inhibition of LIMK activity may represent an attractive new strategy to control and inhibit platelet function; particularly the formation of stable platelet aggregates and thus stable thrombi.

cell biology↗