Detection and identification of mutations and metabolic pathways associated with host adaptation in the pangenome of Salmonella

L’évolution du genre Salmonella a conduit à l’apparition d’espèces et de sous-lignées adaptées à différents hôtes jouant un rôle majeur dans la compréhension des mécanismes biologiques de l’adaptation bactérienne. En raison du lourd fardeau sanitaire et socio-économique que représente les salmonelloses, le genre Salmonella est donc contrôlé par des laboratoires hospitaliers et de sécurité alimentaire. Nous avons donc développé deux approches analytiques permettant de détecter et identifier les mutations associées à l’adaptation aux hôtes de Salmonella sans a priori sur les éléments génomiques explicatifs, en identifiant les variants du coregénome fixés aux nœuds de reconstruction phylogénomique ou en identifiant les mutations pangénomiques associées à ces hôtes indépendamment des sous-lignées bactériennes considérées (c.à.d. GWAS). Ces deux approches ont été couplées à des études d’enrichissement des voies métaboliques correspondantes (c.à.d. GOAE). En raison de pressions de sélection de l’environnement naturel des animaux, de leurs régimes alimentaires, ou des supplémentations administrées par l’Homme, nos résultats montrent que l’adaptation aux hôtes de Salmonella a pu avoir lieu au sein ou entre les sous-lignées. Ces résultats renforcent la nécessité d’intégrer des sous-lignées clonales et panmictiques afin d’identifier les mutations causales associées à l’adaptation aux hôtes. Dans un contexte de contrôle des TIAC tout au long de la chaîne alimentaire, l’identification de ces mutations récentes permettrait d’améliorer les modèles d’attribution des sources animales de Salmonella et de confirmer des résultats d’investigations de TIAC à l’échelle génomique.The evolution of the genus Salmonella has led to the appearance of species and sub-lineages adapted to different hosts that have a major role in understanding the biological mechanisms of bacterial adaptation. Due to the heavy health and socio-economic burden of salmonellosis, the genus Salmonella is therefore controlled by hospital and food safety laboratories. We have therefore developed two analytical approaches to detect and identify mutations associated with Salmonella host adaptation without a priori on the explanatory genomic elements, identifying the fixed coregenome variants at each node of the phylogenomic inference or identifying pangenomic mutations associated with host adaptation independently of considered bacterial sublineages (GWAS). These two approaches have been linked to the enrichment of corresponding metabolic pathways (GOEA). Because of selection pressures from natural environment of animals, their feeding diets or supplements administered by humans, our results show that the host adaptation of Salmonella may have occurred inside sublineages or between them. These results reinforce the necessity to integrate clonal and panmictic sublineages in order to identify causal mutations associated with host adaptation. In a context of FBO control throughout the food chain, the identification of its recent mutations would improve the attribution models of Salmonella animals’sources and confirm the results of FBO investigations at genomic scale

First gene-ontology enrichment analysis based on bacterial coregenome variants: insights into adaptations of Salmonella serovars to mammalian- and avian-hosts

Abstract Background Many of the bacterial genomic studies exploring evolution processes of the host adaptation focus on the accessory genome describing how the gains and losses of genes can explain the colonization of new habitats. Consequently, we developed a new approach focusing on the coregenome in order to describe the host adaptation of Salmonella serovars. Methods In the present work, we propose bioinformatic tools allowing (i) robust phylogenetic inference based on SNPs and recombination events, (ii) identification of fixed SNPs and InDels distinguishing homoplastic and non-homoplastic coregenome variants, and (iii) gene-ontology enrichment analyses to describe metabolic processes involved in adaptation of Salmonella enterica subsp. enterica to mammalian- (S. Dublin), multi- (S. Enteritidis), and avian- (S. Pullorum and S. Gallinarum) hosts. Results The ‘VARCall’ workflow produced a robust phylogenetic inference confirming that the monophyletic clade S. Dublin diverged from the polyphyletic clade S. Enteritidis which includes the divergent clades S. Pullorum and S. Gallinarum (i). The scripts ‘phyloFixedVar’ and ‘FixedVar’ detected non-synonymous and non-homoplastic fixed variants supporting the phylogenetic reconstruction (ii). The scripts ‘GetGOxML’ and ‘EveryGO’ identified representative metabolic pathways related to host adaptation using the first gene-ontology enrichment analysis based on bacterial coregenome variants (iii). Conclusions We propose in the present manuscript a new coregenome approach coupling identification of fixed SNPs and InDels with regards to inferred phylogenetic clades, and gene-ontology enrichment analysis in order to describe the adaptation of Salmonella serovars Dublin (i.e. mammalian-hosts), Enteritidis (i.e. multi-hosts), Pullorum (i.e. avian-hosts) and Gallinarum (i.e. avian-hosts) at the coregenome scale. All these polyvalent Bioinformatic tools can be applied on other bacterial genus without additional developments

L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

30 août 19241924/08/30 (A25,N8659)