Biology subjects

Gaudin, N.

Publications and source records attributed to Gaudin, N..

3 recordsLinked to original sources

bioRxiv2026

Calcium signals natural transformation in Acinetobacter baumannii

The acquisition of resistance to antibiotics in the opportunistic pathogen Acinetobacter baumannii may be linked to its capacity to undergo natural transformation. This mode of horizontal gene transfer relies on the import of extracellular DNA and its chromosomal integration by homologous recombination. Type IV pilus activity initiates the capture of extracellular DNA, which is then transported to the cytoplasm for recombination in the chromosome. While most Acinetobacter baumannii strains are transformable, the conditions allowing the expression of type IV pilus and other transformation genes remain largely unexplored. By investigating transformation-permissive conditions, we uncovered that calcium is a potent inducer of natural transformation. Type IV pilus genes and other transformation-specific genes (comEA, dprA) are upregulated by submillimolar concentrations of calcium ions, in a growth phase-dependent manner. In contrast, sodium chloride represses expression of pilA, counteracting the calcium-dependent induction, explaining the reported absence of transformation in NaCl-containing medium (such as LB). Independently of transcriptional induction, calcium ions also directly bind the type IV pilus through the calcium-dependent adhesin PilY1. Our data support a model in which calcium strengthens the interaction of PilY1 with the minor pilin complex, increasing pilus dynamics and subsequent pilus-dependent DNA capture. Hence, calcium signals natural transformation through both transcriptional and structural activation of type IV pilus. In addition to providing new insights into the regulation of natural transformation in A. baumannii this work led us to establish a protocol for genetic engineering of A. baumannii by natural transformation. ImportanceAcinetobacter baumannii is a nosocomial pathogen considered a critical research priority due to its resistance to last resort antibiotics. Understanding how A. baumannii evolves and acquires resistance to antibiotics is thus of prime importance. This species is capable of natural transformation, a means to acquire and spread genetic information, including antibiotic resistance genes. However, the conditions under which this process is active in this species remain elusive. We identify calcium ions as potent inducers of natural transformation and propose a model of the signaling of natural transformation by calcium ions. This opens the way for further investigations into the contribution of natural transformation to acquisition of antibiotic resistance. In addition, it provides an efficient way to genetically manipulate most A. baumannii strains.

microbiology↗

bioRxiv2024

A peptide-neurotensin conjugate that crosses the blood-brain barrier induces pharmacological hypothermia associated with anticonvulsant, neuroprotective and anti-inflammatory properties following status epilepticus in mice

Preclinical and clinical studies show that mild to moderate hypothermia is neuroprotective in sudden cardiac arrest, ischemic stroke, perinatal hypoxia/ischemia, traumatic brain injury and seizures. Induction of hypothermia largely involves physical cooling therapies, which induce several clinical complications, while some molecules have shown to be efficient in pharmacologically induced hypothermia (PIH). Neurotensin (NT), a 13 amino-acid neuropeptide that regulates body temperature, interacts with various receptors to mediate its peripheral and central effects. NT induces PIH when administered intracerebrally. However, these effects are not observed if NT is administered peripherally, due to its rapid degradation and poor passage of the blood brain barrier (BBB). We conjugated NT to peptides that bind the low-density lipoprotein receptor (LDLR) to generate "vectorized" forms of NT with enhanced BBB permeability. We evaluated their effects in epileptic conditions following peripheral administration. One of these conjugates, VH-N412, displayed improved stability, binding potential to both the LDLR and NTSR-1, rodent/human cross-reactivity and improved brain distribution. In a mouse model of kainate (KA)-induced status epilepticus (SE), VH-N412 elicited rapid hypothermia associated with anticonvulsant effects, potent neuroprotection and reduced hippocampal inflammation. VH-N412 also reduced sprouting of the dentate gyrus mossy fibers and preserved learning and memory skills in the treated mice. In cultured hippocampal neurons, VH-N412 displayed temperature-independent neuroprotective properties. To the best of our knowledge, this is the first report describing the successful treatment of SE with PIH. In all, our results show that vectorized NT may elicit different neuroprotection mechanisms mediated either by hypothermia and/or by intrinsic neuroprotective properties.

neuroscience↗

bioRxiv2022

Length-limitation of astral microtubules orients cell divisions in intestinal crypts

Planar spindle orientation is critical for epithelial tissue organization, and generally instructed from the long cell shape axis or cortical polarity domains. We introduced mouse intestinal organoid crypts to study spindle orientation in a monolayered mammalian epithelium. Although spindles were planar in this tissue, mitotic cells remained elongated along the apico-basal axis and polarity complexes were segregated to basal poles, so that spindles oriented in an unconventional manner, orthogonal to both polarity and geometric cues. Using high-resolution 3D imaging, simulations, cell shape and cytoskeleton manipulations, we show that planar divisions resulted from a length-limitation in mitotic-phase astral microtubules which precludes them from interacting with basal polarity, and oriented spindles from the local geometry of apical domains. Accordingly, lengthening microtubules affected spindle planarity, cell positioning and crypt arrangement. We conclude that microtubule length regulation may serve as a key mechanism for spindles to sense local cell shapes and tissue forces to preserve mammalian epithelial architecture.

developmental biology↗