Biology subjects

Lerouxel, O.

Publications and source records attributed to Lerouxel, O..

3 recordsLinked to original sources

bioRxiv2026

Selective inhibition of anaerobic ubiquinone biosynthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a metabolically versatile opportunistic pathogen capable of adapting to diverse and challenging environments, including the oxygen- and nutrient-limited conditions encountered during chronic infections. Its ability to utilize a broad range of carbon sources and to switch from aerobic to anaerobic respiration contributes to its persistence within the host and its resilience to therapeutic interventions. In particular, denitrification enables P. aeruginosa to grow under oxygen-limited conditions by using nitrate and nitrite as alternative electron acceptors, a process particularly relevant in biofilms and chronic infections such as cystic fibrosis. Ubiquinone (UQ) is essential for respiratory metabolism in P. aeruginosa, which possesses two distinct UQ biosynthetic pathways that ensure UQ production across a broad range of oxygen concentrations. Recent studies have identified the O2-independent UQ biosynthetic pathway as a key determinant of chronic infection. Because this pathway is restricted to a limited group of bacteria, we hypothesized that its selective inhibition could represent a strategy to specifically target P. aeruginosa under anaerobic conditions. To test this hypothesis, we screened analogues of 4-hydroxybenzoic acid (4-HB), the earliest precursor of the UQ biosynthetic pathway, and identified 4-aminobenzoic acid, also known as para-aminobenzoic acid (pABA), as a potential inhibitor. pABA primarily affects the anaerobic metabolism of P. aeruginosa by acting as a competing substrate for UQ biosynthetic enzymes, thereby interfering with UQ biosynthesis. This inhibitory effect positions pABA as a valuable tool for investigating, and potentially targeting, anaerobic metabolism in P. aeruginosa.

microbiology↗

bioRxiv2025

Global distribution of isoprenoid quinones across Bacteria

Isoprenoid quinones represent a class of redox lipids involved in many critical cellular functions, including ATP synthesis through electron transport chains. They thus occupy a pivotal role in the bioenergetics of all three domains of life. The diversity of quinone types observed across microbial taxa has long supported their use as chemotaxonomic markers in microbial systematics. More recently, variations in quinone repertoires have been linked to metabolic adaptations and a novel quinone was discovered. Despite a revived interest in the role of quinones, a unified perspective on the distribution of quinones in Bacteria is currently lacking. In this study, quinone biosynthetic pathways were systematically annotated in 26,264 high quality genomes of bacterial species, and specific information on quinones produced by over 6,000 bacterial species was extracted by text mining the abstracts of thousands of articles. The results were mapped onto a phylogenetic tree, providing the most comprehensive overview of quinone distribution in Bacteria to date. This enabled us to highlight the surprisingly dynamic evolutionary history of the two menaquinone-producing pathways. Moreover, the identification and experimental validation of a deeply branching ubiquinone pathway in Desulfobacterota represents the first occurrence of such a pathway outside the Pseudomonadota and provides insights into the nature of the ancestral UQ pathway. The updated compendium of bacterial quinones is a valuable resource to facilitate the prediction of quinone structural features from genomic data, to establish correlations between quinone structures and cellular traits, and to explore the evolution of quinone repertoires in connection with the diversification of microbial metabolisms.

microbiology↗

bioRxiv2022

Building artificial plant cell wall on lipid bilayer by assembling polysaccharides and engineered proteins

The cell wall constitutes a fundamental structural component of plant cells, providing them with mechanical resistance and flexibility. Mimicking that wall is a critical step in the conception of an experimental model of the plant cell. The assembly of cellulose/hemicellulose in the form of cellulose nanocrystals and xyloglucans as a representative model of the plant cell wall has already been mastered, however, those models lacked the pectin component. In this work, we used an engineered chimeric protein designed for bridging pectin to the cellulose/hemicellulose network, therefore achieving the assembly of complete cell wall mimics. We first engineered proteins, i.e. carbohydrate-binding module from Ruminococcus flavefaciens able to bind oligo-galactorunan, resulting in high-affinity polygalacturonan receptors with Kd in the micromolar range. A Janus protein, with cell wall gluing property, was then designed by assembling this CBM with a Ralstonia solanacearum lectin specific for fucosylated xyloglucans. The resulting supramolecular architecture is able to bind fucose-containing xyloglucans and homogalacturonan ensuring high affinity for both. A two-dimension assembly of an artificial plant cell wall was then built first on synthetic polymer and then on supported lipid bilayer. Such artificial cell wall can serve as a basis for the development of plant cell mechanical models and thus deepen the understanding of the principles underlying various aspects of plant cells and tissues. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=123 HEIGHT=200 SRC="FIGDIR/small/501355v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@18af594org.highwire.dtl.DTLVardef@ec3dorg.highwire.dtl.DTLVardef@95d44aorg.highwire.dtl.DTLVardef@a47bea_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗