Biology subjects

Buisson, A.

Publications and source records attributed to Buisson, A..

6 recordsLinked to original sources

bioRxiv2026

Type 6 secretion systems of adherent-invasive Escherichia coli isolated from Crohn's disease patients shape intestinal microbiota.

Adherent Invasive Escherichia coli (AIEC) colonize the ileal mucosa of Crohn's disease patients. Among bacterial virulence factors potentially implicated, type 6 secretion systems (T6SS) are molecular machineries sending effectors in prokaryotic or eukaryotic target cells. Two T6SS have been reported in AIEC LF82 reference strain. Here, we show that T6SS genes are more prevalent in Crohn's disease patients' microbiota compared to healthy controls, and that T6SS are more frequent in AIEC pathovar compared to E. coli in general and associated with FimH pathoadaptive polymorphism. The use of an in vitro gastrointestinal system coupled with T6SS promoter reporter assay highlighted expression of LF82 T6SS under gastrointestinal conditions, with a major role for bile salts. In mice infected with AIEC LF82 versus T6SS-deleted mutants, T6SS showed a functional impact in modulating the composition of mucosa-associated gut microbiota. Thus, AIEC may use their T6SS to compete with endogenous microbiota to colonize host mucosa.

microbiology↗

bioRxiv2025

The BMP4-BMPR1A axis represses BRCA1, inducing BRCAness in mammary stem cells and contributing to tumor initiation in basal-like breast cancer

Basal-like breast cancer (BLBC) is an aggressive subtype frequently characterized by homologous recombination deficiency (HRD) and BRCAness, even in the absence of BRCA1 mutations. Here, we identify the BMP4-BMPR1A signaling axis as a novel regulator of BRCA1 expression and a driver of BRCAness in non-transformed immature mammary cells. We observed that high BMPR1A expression is correlated with low BRCA1 levels and poor BLBC prognosis in patients. We show that exposure to BMP4 induces BRCA1 transcriptional repression via BMPR1A, promoting a basal differentiation and impairing homologous recombination. This results in increased sensitivity to PARP inhibitors (PARPi) and accumulation of genetically-unstable, immature cells. In addition, long-term BMP4 stimulation or BMPR1A overexpression induced transformation. Our findings uncover a mechanism by which the tumor microenvironment may contribute to BLBC initiation through BMP4-induced suppression of BRCA1, and highlight BMP signaling and the resulting BRCAness as a therapeutic vulnerability in wild-type BRCA1 BLBCs.

cancer biology↗

bioRxiv2024

E. coli associated with Crohn's disease exhibit distinct strategies to colonize macrophages

Patients with Crohns disease exhibit abnormal colonization of the intestine by Proteobacteria, particularly the adherent-invasive Escherichia coli (AIEC) group. These bacteria are predominant in the mucus, adhere to epithelial cells, colonize them, and survive inside macrophages. We recently demonstrated that the acclimation of strain LF82 to phagolysosomal stress occurs in two distinct steps: first, a replication halt producing stress- tolerant persisters, and second, a replication phase that leads to the formation of Intracellular Bacterial Communities (IBC) organized with a biofilm-like matrix. Given the significant genomic diversity among strains with the AIEC phenotype, we conducted a comparative analysis of the genomes and macrophage colonization characteristics of 13 AIEC strains collected from patients during a clinical study conducts by the CHU of Clermont-Ferrand. Our results demonstrate that IBCs serve as replicative niches for all AIEC strains within macrophages. However, these strains form IBCs using different strategies, including varying levels of phagosome detoxification, distinct biofilm characteristics, and diverse macrophage responses. Our study reveals a strong positive correlation between vacuole acidification and persister induction that explains intracellular survival of the different strains. In addition, we revealed distinct AIEC dissemination strategies outside macrophages, which may contribute to the propagation of inflammation in the human host. These findings highlight that research on pathogens and pathobionts with plastic genomes should not rely solely on a few laboratory models.

microbiology↗

bioRxiv2021

Impaired α-tubulin re-tyrosination leads to synaptic dysfunction and is a feature of Alzheimer's disease

In neurons, dynamic microtubules play regulatory roles in neurotransmission and synaptic plasticity. While stable microtubules contain detyrosinated tubulin, dynamic microtubules are composed of tyrosinated tubulin, suggesting that the tubulin tyrosination/detyrosination (Tyr/deTyr) cycle modulates microtubule dynamics and synaptic function. In the Tyr/deTyr cycle, the C-terminal tyrosine of -tubulin is re-added by tubulin-tyrosine-ligase (TTL). Here we show that TTL+/- mice exhibit decreased tyrosinated microtubules, synaptic plasticity and memory deficits, and that reduced TTL expression is a feature of sporadic and familial Alzheimers disease (AD), with human APPV717I neurons having less dynamic microtubules. We find that spines visited by dynamic microtubules are more resistant to Amyloid{beta}1-42 and that TTL, by promoting microtubule entry into spines, prevents A{beta}1-42-induced spine pruning. Our results demonstrate that the Tyr/deTyr cycle regulates synaptic plasticity, is protective against spine injury, and that tubulin re-tyrosination is lost in AD, providing evidence that a defective Tyr/deTyr cycle may contribute to neurodegeneration.

neuroscience↗

bioRxiv2021

Astrocyte-neuron interplay is critical for Alzheimer's disease pathogenesis and is rescued by TRPA1 channel blockade

BackgroundThe sequence of cellular dysfunctions in preclinical Alzheimers disease must be understood if we are to plot new therapeutic routes. Hippocampal neuronal hyperactivity is one of the earliest events occurring during the preclinical stages of Alzheimers disease in both humans and mouse models. The most common hypothesis describes amyloid {beta} accumulation as the triggering factor of the disease but the effects of such accumulation and the cascade of events leading to cognitive decline remain unclear. In mice, we previously showed that amyloid {beta}-dependent TRPA1 channel activation triggers hippocampal astrocyte hyperactivity, subsequently inducing hyperactivity in nearby neurons. In this work, we investigated the potential protection brought by an early chronic pharmacological inhibition of TRPA1 channel on Alzheimers disease progression. MethodsWe administered a specific inhibitor of TRPA1 channel (HC030031) intraperitoneally from the onset of amyloid {beta} overproduction in the APP/PS1-21 mouse model of Alzheimers disease. We characterized short-, medium-, and long-term effects of this chronic pharmacological TRPA1 blockade on Alzheimers disease progression at functional (astrocytic and neuronal activity), structural, biochemical, and behavioural levels. ResultsOur results revealed that the first observable disruptions in the Alzheimers disease transgenic mouse model used correspond to aberrant hippocampal astrocyte and neuron hyperactivity. We showed that chronic TRPA1 blockade normalizes astrocytic activity, avoids perisynaptic astrocytic process withdrawal, prevents neuronal dysfunction, preserves structural synaptic integrity and strengthens the glial plaque barrier. These protective effects preserved spatial working-memory in this Alzheimers disease mouse model. ConclusionThe toxic effect of amyloid {beta} on astrocytes triggered by TRPA1 channel activation is pivotal to Alzheimers disease progression. TRPA1 blockade prevent irreversible neuronal dysfunction, making this channel a potential therapeutic target to promote neuroprotection.

neuroscience↗

bioRxiv2020

ALG-2 interacting protein-X (Alix) is required for activity-dependent bulk endocytosis at brain synapses

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity dependent bulk endocytosis (ADBE). Alix (ALG-2 interacting protein X)/ PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrin-independent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with, and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ABDE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix alters synaptic recovery during physiological or pathological repeated stimulations.

neuroscience↗