Biology subjects

Billard, E.

Publications and source records attributed to Billard, E..

5 recordsLinked to original sources

bioRxiv2026

Insights Into an Antibacterial Type VI Membrane-Disrupting Effector Of Adherent Invasive Escherichia coli

Adherent Invasive Escherichia coli (AIEC) strains are associated with ileal Crohn's disease and may contribute to intestinal dysbiosis through antibacterial competition. The AIEC reference strain LF82 encodes two type VI secretion systems (T6SSs), a contractile machine that injects an effector-loaded needle made of Hcp, VgrG and PAAR into neighbouring rivals, favoring niche colonization. LF82 T6SSs harbour several putative antibacterial toxin-immunity modules. Here we characterize the T6SS-1 encoded TmeAIEC, a PAAR-fused T6SS effector carrying a C-terminal Tme domain, hallmark of Tme (Type VI membrane disrupting effector) toxins, and its DUF1240-like immunity protein TmiAIEC. When heterologously produced in E. coli K-12 as well as in E. coli and Citrobacter clinical isolates, TmeAIEC is toxic only upon periplasmic targeting, and its toxicity is neutralized by TmiAIEC. Periplasmically-targeted TmeAIEC inserts into the inner membrane, collapses the proton motive force and increases cell permeability, consistent with a membrane-disrupting activity. Mutational analyses coupled to functional assays identified a predicted hydrophobic transmembrane segment and a conserved aspartate residue within the Tme domain as key determinants for TmeAIEC toxicity. These findings establish TmeAIEC/TmiAIEC as a functional T6SS toxin-immunity pair and reveal conserved determinants underlying the activity of Tme-family membrane-disrupting effectors.

microbiology↗

bioRxiv2025

PhytClust: efficient and optimal node clustering in phylogenetic trees

Phylogenetic trees play a fundamental role in elucidating evolutionary relationships among taxa. Clustering taxa remains a major challenge across diverse biological domains such as cancer genomics, microbial systematics, and phylogenomics. Several methods partition taxa in phylogenetic trees into clusters, but these approaches face key limitations. Many rely on user-defined distance thresholds, whose choice often depends on prior knowledge and may be difficult to justify consistently across datasets. More broadly, existing methods often differ in how clusters are defined and commonly rely on heuristics or user-specified criteria to make the search space tractable for large trees. Here, we present PhytClust, a threshold-free algorithm that partitions trees into monophyletic subtrees (clusters) by identifying groups of taxa with low within-cluster dispersion. For a fixed number of clusters, PhytClust finds the exact global optimum under this objective and then selects the optimal number of clusters using a cluster-validity index. The resulting partitions are reproducible and reflect both tree topology and branch lengths. In simulated datasets, PhytClust outperforms existing methods in both speed and accuracy and scales to trees with more than a hundred thousand taxa. We apply PhytClust across cancer genomics, avian phylogenomics, bacterial and archaea phylogenetics, and plant genomics to demonstrate PhytClusts varied applicability. By providing a standardized method for taxa clustering within phylogenetic trees, PhytClust yields reproducible, optimal and computationally efficient clusters.

evolutionary biology↗

bioRxiv2025

Symptom observation underestimates co-infections: insight from viral and bacterial diseases in rice fields in Burkina Faso

Co-occurrence of multiple diseases and co-infection of individual plants by various pathogens have potential epidemiological and evolutionary implications. Based on previous information on the co-occurrence of the rice yellow mottle disease (caused by the rice yellow mottle virus, RYMV) and bacterial leaf streak (BLS, due to Xanthomonas oryzae pv. oryzicola, Xoc) in Burkina Faso, and experimental evidence of interactions between the pathogens causing these two diseases, we aimed to monitor the two pathogens more intensively in farmers rice fields. To this purpose, we selected fields showing both types of symptoms to maximize the chance of observing co-infections at the plant scale. We performed observations and sampling in two sites over two consecutive years. Over a global dataset of 1666 samples, 1341 were symptomatic. Although the sampling design aimed to observe co-infections, only 37 of these samples (2.8%) were annotated as presenting both yellow mottle and BLS symptoms. The samples were then subjected to a newly designed molecular detection test that specifically amplifies both the virus (RYMV) and the bacteria (Xo). This revealed that 166 samples, i.e. 12.4% of symptomatic samples, were co-infected by RYMV and Xo, hence showing that symptom observation in the field greatly underestimates co-infection levels. Combining these data with a previously published dataset, we estimated that up to 1-4% of all plants in disease hotspots are simultaneously infected by the two pathogens. Further research on multiple infections would benefit from longitudinal surveys over the crop growing season rather than such a cross-sectional study.

plant biology↗

bioRxiv2023

Dynamics of the rice yellow mottle disease in western Burkina Faso: epidemic monitoring, spatio-temporal variation of viral diversity and pathogenicity in a disease hotspot

The rice yellow mottle virus (RYMV) is a model in plant virus molecular epidemiology and phylogeography, with the reconstruction of historical introduction routes at the scale of the African continent. However, information on patterns of viral prevalence and viral diversity over multiple years at local scale remain scarce, in spite of potential implications for crop protection. Here we describe a five-years monitoring of RYMV prevalence in six sites from western Burkina Faso. This study confirmed one irrigated site as a disease hotspot, and found two rainfed lowland sites with occasional high prevalence levels. Within studied field, a pattern of disease aggregation was evidenced at a five-meter distance, as expected for a mechanically transmitted virus. Next, we monitored RYMV genetic diversity in the irrigated disease hotspot site, revealing a high viral diversity, with the current coexistence of various distinct genetic groups at the site-scale (irrigated perimeter of ca. 520 ha), and also within various specific fields (25 meters side). One genetic lineage, named S1bzn, is the most recently introduced group and increased in frequency over the studied period. Its genome results from a recombination between two other lineages. Finally, experimental work evidenced no differences between three rice varieties cultivated in Burkina Faso in terms of resistance level, and no statistical effect of RYMV genetic group on symptom expression and viral load. We found however, that infection outcome depended on the specific RYMV isolate, with various isolates from the lineage S1bzn found to be particularly aggressive, including one accumulating at highest level. Overall, this study documents a case of high viral prevalence and high viral diversity, with the co-occurrence of divergent genetic lineages at small geographic scale. A recently introduced lineage, that includes viral isolates with high symptoms and accumulation in controlled conditions, could be recently rising though natural selection. Following up the monitoring of RYMV genetic and pathogenic diversity in the area is required to confirm this trend and further understand the factors driving the maintenance of viral diversity at local scale.

evolutionary biology↗

bioRxiv2020

Membrane-tethered peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as allosteric biased ligands

Over the last decade, the urotensinergic system has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases and also cancer. Significant investment toward the development of clinically relevant UT ligands for therapeutic intervention has been made but have met little to no success to date. The UT system, which has yet to be effectively targeted, therefore remains to be therapeutically exploited. The discovery of allosteric sites that allow modulation of receptor activity will increase the searchable chemical space against a disease-relevant target. Pepducins and other lipidated peptides have been used as both mechanistic probes and potential therapeutics. Therefore, pepducins derived from the human urotensin II receptor might represent unique tools to generate signaling bias and study UT signaling networks. Two hUT-derived pepducins, derived from the second and the third intracellular loop of UT, respectively, have been synthesized and pharmacologically characterized. Our results demonstrated that hUT-Pep2 and [Trp1, Leu2]hUT-Pep3 acted as biased ago-allosteric modulators, triggered ERK1/2 phosphorylation and to a lesser extent, IP1 production, stimulated cell proliferation yet were devoid of contractile activity. Interestingly, both hUT-derived pepducins were able to modulate hUII- and URP-mediated contraction albeit to different extents. These new derivatives represent unique tools to reveal the intricacies of hUT signaling and also a novel avenue to design allosteric ligands selectively targeting UT signaling that could prove to be useful for the treatment of hUT-associated diseases.

pharmacology and toxicology↗