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O025 - MECHANISMS OF VIRULENCE REGULATION AND GLOBAL DISTRIBUTION OF VACCINE CANDIDATE ANTIGENS IN THE HIGH VIRULENT STREPTOCOCCUS PNEUMONIAE STRAINS (ID 285)
Metabolic flexibility is a prerequisite for successful transition of Streptococcus pneumoniae (Spn) from colonizing to invasive state. The aim of this study was to investigate the common metabolic features of pneumococcus invasive strains and propose vaccine candidate antigens.
The dataset (1058 PubMLST Spn strains) was stratified by genotype and included all known epidemically significant invasive and non-invasive clones. Genomes (495) were analyzed with GenomeComparator. Core gene variant matrix was used to run machine learning algorithms (RandomForest, XGBoost) to find gene variants associations with genotypes and invasiveness. Topology and composition of phylogenetic trees clusters comparison was performed using Visual TreeCmp.
Phylogenetic analysis (based on MLST concatenates) revealed clustering of global pneumococcal population into the three groups (A, B1, B2), which may be associated with virulence. 181 genes were significant for the formation of A/B1/B2 groups: the components of various metabolic pathways (fatty acid biosynthesis, phenylalanine, biotin, arginine, galactose, fructose, mannose, purine bases, pyruvate, cysteine and methionine, alanine, aspartate and glutamate) and different virulence factors. Invasiveness is regulated by network of interacting genes variants: strH (exo-β-D-N-acetylglucosaminidase), carbohydrate metabolism components (gnd, dexB), aromatic amino acid synthesis pathways (aroE), relA regulatory gene (GTP pyrophosphokinase), peptidoglycan synthesis and cell division genes (murD, pbp1A), regulatory genes of polysaccharide capsule expression (wzg-wzh-wze).
Carbohydrates and aromatic amino acids metabolism pathways are involved in the regulation of cellular processes and phenotypic features of pneumococcus, including virulence. We achieved the list of vaccine candidates, which must be confirmed by reverse vaccinology.