Biology subjects

Ginet, N.

Publications and source records attributed to Ginet, N..

4 recordsLinked to original sources

bioRxiv2024

HieVi: Protein Large Language Model for proteome-based phage clustering

Viral taxonomy is a challenging task due to the propensity of viruses for recombination. Recent updates from the ICTV and advancements in proteome-based clustering tools highlight the need for a unified framework to organize bacteriophages (phages) across multiscale taxonomic ranks, extending beyond genome-based clustering. Meanwhile, self-supervised large language models, trained on amino acid sequences, have proven effective in capturing the structural, functional, and evolutionary properties of proteins. Building on these advancements, we introduce HieVi, which uses embeddings from a protein language model to define a vector representation of phages and generate a hierarchical tree of phages. Using the INPHARED dataset of 24,362 complete and annotated viral genomes, we show that in HieVi, a multi-scale taxonomic ranking emerges that aligns well with current ICTV taxonomy. We propose that this method, unique in its integration of protein language models for viral taxonomy, can encode phylogenetic relationships, at least up to the family level. It therefore offers a valuable tool for biologists to discover and define new phage families while unraveling novel evolutionary connections.

genomics↗

bioRxiv2024

Antibiotic-Induced Morphological Changes Enhance Phage Predation: A Mathematical Model of Plaque Formation in Structured Environments

A distinctive manifestation of phage infection in solid media is the appearance of lysis plaques, which correspond to the circular thinning of a bacterial lawn. During plaque formation, successive cycles of phage replication generally take place from a single point of infection and spread radially in a matrix of immobilized bacterial hosts. Many different factors affect plaque size, such as the composition and the reticulation of the propagation matrix, the characteristics of the phage, but also parameters related to the physiology of the bacterial host. Since combined administration of both antibiotics and phages is a common practice during compassionate treatments, our research focuses on the effects of antibiotics on phage predation, which can be of crucial importance for the therapeutic applications of phages. It has been previously observed that the presence of antibiotics at sublethal concentrations can affect drastically bacterial physiology, allowing phages to spread more rapidly and resulting in better bacterial eradication. Previous experimental work has focused on the phage characteristics that influence plaque size. However, as plaque formation is strongly influenced by host growth dynamics, a comprehensive model integrating both the host growth and phage infection parameters is required. In this work, we suggest that plaque enlargement is linked to morphological changes of the host that have an impact on the rate of epidemic propagation and certainly on phage diffusion into the matrix. To support this hypothesis, we characterized the growth parameters of two different phages and bacteria in semi-solid media in the presence of various antibiotics. By combining these data, we have produced a mathematical model that accounts for these observations and explains the increase in plaque size when the host morphology is affected. Significance StatementThis study provides new insights into the phenomenon of Phage-Antibiotic Synergy (PAS) by demonstrating that antibiotic-induced morphological changes in bacterial hosts play a critical role in enhancing phage propagation in structured environments. By linking these morphological alterations--such as cell filamentation and bloating--to increased lysis plaque size, the research underscores the importance of host dynamics in phage therapy. The development of a mathematical model integrating both host growth and phage infection parameters offers a novel framework for understanding and optimizing phage-based treatments in the presence of antibiotics, potentially improving therapeutic outcomes.

microbiology↗

bioRxiv2022

Genetic mining of newly isolated Salmophages for phage therapy

I.Salmonella enterica - a Gram negative zoonotic bacterium - is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. Main reservoirs are found in poultry farms but also in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here we aimed at deciphering and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. We finally searched for useful functions for phage therapy such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRIPSR proteins. We thus were able to genetically characterized nine virulent phages and one temperate phage and identified putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol.

microbiology↗

bioRxiv2022

Pleiotropic effects on E. coli physiology of the AraC-like regulator from prophage origin, AppY

Bacterial genome diversity is largely due to prophages, which are viral genomes integrated into the genomes of bacteria. Most prophage genes are silent, but those that are expressed can provide unexpected properties to their host. Using as a model E. coli K-12, that carries 9 defective prophages in its genome, we aimed at highlighting the impact of viral genes on host physiology. We focused our work on AppY, a transcriptional regulator encoded on the DLP12 prophage. By performing RNA-Seq experiments, we showed that AppY production modulates the expression of more than 200 genes; among them, 13 were identified by ChIP-Seq as direct AppY targets. AppY directly and positively regulates several genes involved in the acid stress response including the master regulator gene gadE, but also nhaR and gadY, two genes involved in biofilm formation. Moreover, AppY indirectly and negatively impacts bacterial motility by favouring the degradation of FlhDC, the master regulator of the flagella biosynthesis. As a consequence of these regulatory effects, AppY increased acid stress resistance and biofilm formation while also causing a strong defect in motility. We therefore demonstrate here that AppY is a central regulator from phage origin that controls the expression of bacterial master regulators to provide benefits to E. coli under stress conditions. Our research shed light on the importance to consider the genetic dialogue occurring between prophages and bacteria to fully understand bacterial physiology.

microbiology↗