Biology subjects

Hendrickx, E.

Publications and source records attributed to Hendrickx, E..

4 recordsLinked to original sources

bioRxiv2026

Extreme envelope plasticity drives temperature-dependent morphogenesis in the LPS-free bacterium Sphingobium yanoikuyae

Bacterial growth patterns are generally considered to be constrained and species-specific. Here, we show that Sphingobium yanoikuyae exhibits exceptional plasticity in envelope architecture and morphogenesis supported by a glycosphingolipid (GSL)-based outer membrane and an atypical peptidoglycan structure. At 30{degrees}C, cells expand asymmetrically via a rare bipolar envelope synthesis mode, whereas growth at 37{degrees}C triggers a transition toward longitudinal elongation accompanied by increased outer membrane vesiculation, indicating a reversible reprogramming of morphogenesis under host-relevant temperature. This switch is supported by rapid outer membrane dynamics, including high membrane fluidity and fast redistribution of envelope components. In addition to these pronounced morphological changes, peptidoglycan contains unusually short glycan strands and displays specific temperature-dependent remodeling suggesting that growth plasticity is not only governed by spatial regulation but also by changes in cell wall cross-linking pattern. Genetic analyses further identify essential roles for proteins involved in outer membrane-peptidoglycan and outer membrane-inner membrane coupling, as well as GSL transport systems, and core cell wall synthesis machinery, while revealing extensive redundancy in envelope remodeling enzymes. Together, these results establish S. yanoikuyae as a model for extreme envelope adaptability, where a highly fluid outer membrane and structurally unconventional peptidoglycan enable reversible transitions between distinct growth programs, potentially shaping environmental fitness and host-associated interactions.

microbiology↗

bioRxiv2025

skNAC is a Key Driver of Cardiomyocyte Integrity Against Pathological Cardiac Hypertrophy and Heart Failure

Chronic pressure overload induces cardiac hypertrophy and heart failure through coordinated alterations in proteome homeostasis, metabolism and sarcomere organisation. The muscle-specific -isoform of the nascent polypeptide-associated complex (skNAC) is essential for sarcomere assembly during development, but its role in adult hearts remains largely unknown. Here, we show that skNAC expression is reduced in hypertrophic cardiomyocytes, mouse models of pressure overload, and human hypertrophic hearts, in association with disease severity. Cardiomyocyte-specific skNAC deletion results in basal hypertrophy, systolic dysfunction, and premature death, and exacerbates pressure overload-induced heart failure. At the molecular level, skNAC associates with ribosomes and is required for sarcomere organisation maintenance, while its loss induces autophagy and ultrastructural defects. Integrated transcriptomic and proteomic analyses reveal early downregulation of metabolic gene expression despite increased abundance of corresponding proteins, indicating compensatory metabolic responses. Gain-of-function studies confirm a protective role against hypertrophy. Together, these data establish skNAC as a key regulator of cardiac proteome homeostasis and metabolic adaptation during pathological remodelling.

physiology↗

bioRxiv2025

Upregulation of the AcrAB2NodT efflux pump confers antibiotic resistance at the cost of collateral metal sensitivity

Bacterial resistance to antibiotics (AB) such as {beta}-lactams, fluoroquinolones, and aminoglycosides often emerges through mutations that alter AB targets, reduce membrane permeability, or increase the activity of AB-modifying enzymes and efflux pumps. Yet the physiological costs associated with AB resistance remain poorly understood. In Caulobacter vibrioides, a {Delta}tipR mutant that which constitutively upregulates the RND pump AcrAB2nodT, displays heightened sensitivity to copper (Cu), revealing a physiological vulnerability driven by the energetic burden imposed by excessive efflux activity. Deletion of acrAB2nodT in the {Delta}tipR background restored Cu resistance to wild-type levels, confirming the role of pump overexpression in metal sensitivity. Morphological and microscopy analyses revealed that pump overexpression leads to cell envelope defects and compromised fitness. To disentangle the effects of pump abundance from efflux activity, we engineered an AcrB2 transport-impaired mutant. This variant also rescued Cu resistance, demonstrating that high expression and active transport contribute to the observed toxicity. Notably, this sensitivity was not limited to Cu; the {Delta}tipR mutant also exhibited increased susceptibility to other transition metals, including zinc (Zn), nickel (Ni) and cadmium (Cd), suggesting a broader vulnerability linked to metal stress. Mechanistically, pump overexpression depleted the proton motive force, reduced ATP levels, and impaired motility, all of which are essential for Cu stress adaptation. This physiological tradeoff highlights the importance of precise efflux regulation and reveals a potential therapeutic vulnerability: targeting the cost of pump upregulation could enhance the efficacy of antimicrobial treatments. ImportanceWhile efflux pumps primarily protect bacteria from AB, their excessive activity can impose a fitness cost. This study underscores a crucial tradeoff between resistance and cellular fitness by connecting Cu sensitivity to heightened AcrAB2NodT efflux pump expression in Caulobacter vibrioides. This work challenges the assumption that more efflux always benefits the cell and shows that unregulated pump activity can undermine survival under metal stress. These findings broaden our understanding of bacterial stress physiology and suggest new ways to combat antimicrobial resistance by targeting the hidden costs of resistance mechanisms. Understanding this balance between resistance and fitness opens new perspectives for combination therapy against multidrug-resistant bacteria.

microbiology↗

bioRxiv2025

Synaptic Gpr85 influences cerebellar granule cells electrical properties and light-induced behavior.

GPR85/SREB2 is an exceptionally conserved orphan seven-transmembrane receptor with poorly understood biological function. Here, we combine genetic, imaging, transcriptomic, electrophysiological, and behavioral approaches in zebrafish to uncover the properties and roles of Gpr85 across development and adulthood. We show that, as in mammals, gpr85 is expressed in diverse neuronal populations within the central nervous system, retina and intestine. Using a fluorochrome-tagged Gpr85 construct expressed in native domains, we provide the first in vivo evidence that Gpr85 is enriched at synaptic sites in both the brain and retina. Transcriptomic profiling of cerebellar granule cells lacking Gpr85 reveals gene expression changes consistent with increased neuronal activity. Electrophysiological recordings from cerebellar slices confirm that Gpr85-deficient granule cells exhibit heightened excitability. Functionally, Gpr85 loss enhances light-triggered startle responses in larval zebrafish. Together, these findings position Gpr85 as a synaptically enriched modulator of neuronal excitability and sensory-driven behavior, offering new insight into its roles.

neuroscience↗