ABSTRACT
Introduction: Serratia marcescens is most commonly known as an opportunistic pathogen causing nosocomial infections. It, however, was shown to infect a wide range of hosts apart from vertebrates such as insects or plants as well, being either pathogenic or growth-promoting for the latter. Despite being extensively studied in terms of virulence mechanisms during human infections, there has been little evidence of which factors determine S. marcescens host specificity. On that account, we analyzed S. marcescens pangenome to reveal possible specificity factors. Methods: We selected 73 high-quality genome assemblies of complete level and reconstructed the respective pangenome and reference phylogeny based on core genes alignment. To find an optimal pipeline, we tested current pangenomic tools and obtained several phylogenetic inferences. The pangenome was rich in its accessory component and was considered open according to the Heaps' law. We then applied the pangenome-wide associating method (pan-GWAS) and predicted positively associated gene clusters attributed to three host groups, namely, humans, insects, and plants. Results: According to the results, significant factors relating to human infections included transcriptional regulators, lipoproteins, ABC transporters, and membrane proteins. Host preference toward insects, in its turn, was associated with diverse enzymes, such as hydrolases, isochorismatase, and N-acetyltransferase with the latter possibly exerting a neurotoxic effect. Finally, plant infection may be conducted through type VI secretion systems and modulation of plant cell wall synthesis. Interestingly, factors associated with plants also included putative growth-promoting proteins like enzymes performing xenobiotic degradation and releasing ammonium irons. We also identified overrepresented functional annotations within the sets of specificity factors and found that their functional characteristics fell into separate clusters, thus, implying that host adaptation is represented by diverse functional pathways. Finally, we found that mobile genetic elements bore specificity determinants. In particular, prophages were mainly associated with factors related to humans, while genetic islands-with insects and plants, respectively. Discussion: In summary, functional enrichments coupled with pangenomic inferences allowed us to hypothesize that the respective host preference is carried out through distinct molecular mechanisms of virulence. To the best of our knowledge, the presented research is the first to identify specific genomic features of S. marcescens assemblies isolated from different hosts at the pangenomic level.
ABSTRACT
Salmonella enterica is a bacterial pathogen known to cause gastrointestinal infections in diverse hosts, including humans and animals. Despite extensive knowledge of virulence mechanisms, understanding the factors driving host specificity remains limited. In this study, we performed a comprehensive pangenome-wide analysis of S. enterica to identify potential loci determining preference towards certain hosts. We used a dataset of high-quality genome assemblies grouped into 300 reference clusters with a special focus on four host groups: humans, pigs, cattle, and birds. The reconstructed pangenome was shown to be open and enriched with the accessory component implying high genetic diversity. Notably, phylogenetic inferences did not correspond to the distribution of affected hosts, as large compact phylogenetic groups were absent. By performing a pangenome-wide association study, we identified potential host specificity determinants. These included multiple genes encoding proteins involved in distinct infection stages, e.g., secretion systems, surface structures, transporters, transcription regulators, etc. We also identified antibiotic resistance loci in host-adapted strains. Functional annotation corroborated the results obtained with significant enrichments related to stress response, antibiotic resistance, ion transport, and surface or extracellular localization. We suggested categorizing the revealed specificity factors into three main groups: pathogenesis, resistance to antibiotics, and propagation of mobile genetic elements (MGEs).
