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Ginet, N.

Publications and source records attributed to Ginet, N..

2 recordsLinked to original sources

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↗

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↗