Guilbaud, C. | Search bioRxiv

bioRxiv2026

Acidosis-triggered fatty acid overload induces endothelial cell dysfunction.

Vascular ischemia is characterized not only by hypoxia but also by acidosis, which affects endothelial cells (ECs) due to increased H+ production from glycolysis and a deficit in H+ washout. We recently documented that an acidic environment facilitates the flip-flop transport of the non-ionized form of fatty acids (FAs) across the plasma membrane of cancer cells. In this study, we investigated how acidosis influences the capacity of highly glycolytic ECs to manage FAs and participates to endothelial dysfunction. We first tracked lipid droplet (LD) formation using Oil Red O staining and holotomographic microscopy. Purified monounsaturated oleate but also a mixture of FAs that reflect in vivo serum composition, resulted in dose- and time-dependent LD accumulation through FA transporter-independent mechanisms. Acid-exposed ECs exhibited enhanced mitochondrial respiration fueled by FAs, and endoplasmic reticulum (ER) stress, as indicated by the expression of ATF4 and CHOP. This phenotype was further associated with elevated reactive oxygen species production, which correlated with reduced nitric oxide (NO) availability. FA removal from EC culture media promoted lipolysis from LDs, supported by ATGL lipase induction which however slowed under acidic conditions. While ER stress persisted upon FA washout, NO availability was restored to levels comparable to those in FA-unexposed ECs. This observation coincided with dynamic mobilization of antioxidant defenses in acid-exposed ECs, as evidenced by low levels of reduced glutathione and enhanced cystine uptake, alongside a decrease in carnitine and FA-fueled mitochondrial respiration. Collectively, these data underscore the vulnerability of ECs to passive FA capture promoted by local acidosis, thereby contributing to a silent source of endothelial dysfunction in the postprandial state or during chronic exposure to elevated lipid levels.

cell biology↗

bioRxiv2022

Comparative seasonal abundance and diversity of populations of the Pseudomonas syringae and Soft Rot Pectobacteriaceae species complexes throughout the Durance River catchment from its French Alps sources to its delta

Rivers, creeks, streams are integrators of biological, chemical and physical processes occurring in a catchment linking land cover from the headwaters to the outlet. The dynamics of human and animal pathogens in catchments have been widely studied in a large variety of contexts allowing the optimization of disease risk reduction. In parallel, there is an emerging awareness that crop pathogens might also be disseminated via surface waters especially when they are used for irrigation. However, there are no studies on the extent to which potential plant pathogens are present - nor about their dynamics - along the full course of a catchment. Here we have compared the seasonal dynamics of populations of the Pseudomonas syringae (Psy) and the Soft Rot Pectobacteriaceae (SRP) species complexes along a 270 km stretch of the Durance River from the upstream alpine reaches to the downstream agricultural production areas at the confluence with the Rhone River at Avignon. Among 168 samples collected at 21 sites in fall, winter, spring and summer of 2016 and 2017, Psy strains were detected at all sampling sites and in 156 of the samples at population densities up to 105 bacteria L-1. In contrast, SRP strains were detected in 98 of the samples, mostly from the southern part of the river, at population densities that did not exceed 3 x 104 bacteria L-1. Among the biological and chemical parameters that were characterized at each sampling site, temperature was the only factor that explained a significant amount of the variability in population size for both species complexes. Psy densities decreased with increasing temperature whereas SRP densities increased with increasing temperature. River-borne populations of SRP were composed mainly of Pectobacterium versatile and P. aquaticum that have little known epidemiological importance. Only a few strains of Pectobacterium and Dickeya species reputed for their epidemiological impact were observed. In contrast, Psy populations at all sites were dominated by a genetic lineage of phylogroup 2 known from other studies for its broad host range and its geographic and habitat ubiquity. Our observations suggest that surveillance of river water for SRP could be leveraged to signal diagnostic and management reactions to avoid disease outbreaks. In contrast, the constant presence of Psy throughout the catchment in absence of regular and widespread disease outbreaks due to this group of bacteria suggests that surveillance should focus on future changes in land use, river water conditions and agronomic practices that could destabilize the mechanisms currently holding Psy outbreaks in check.

ecology↗