MECHANISMS OF VIRULENCE REGULATION AND GLOBAL DISTRIBUTION OF VACCINE CANDIDATE ANTIGENS IN THE HIGH VIRULENT STREPTOCOCCUS PNEUMONIAE STRAINS
- Irina A. Tsvetkova, Russian Federation
- Daria V. Likholetova, Russian Federation
- Vladimir V. Gostev, Russian Federation
- Sergey S. Belanov, Finland
- Ekaterina V. Nikitina, Russian Federation
- Olga S. Kalinogorskaya, Russian Federation
- Marina O. Volkova, Russian Federation
- Alexey S. Mokhov, Russian Federation
- Xenia A. Ivanova, Russian Federation
- Ekaterina L. Kalisnikova, Russian Federation
- Anastasia A. Volodina, Russian Federation
- Sergey V. Sidorenko, Russian Federation
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 invasive Spn strains and propose vaccine candidate antigens.
The dataset includes 1058 PubMLST Spn strains. MLST concatenates were used to build maximum likelihood phylogeny. Sequence clusters (SCs) were identified with RhierBAPS. Genomes (n=512) were analyzed with GenomeComparator. The resulting gene variant matrix was used to run classification algorithm to find associations of gene variants with genotypes and invasiveness. GWAS was performed with Samtools mpileup.
Pneumococcal population was clustered into three groups (A,B1,B2) (Fig.1,2). Isolates from blood were more prevalent in B2 group. Clusterization was based on AccC, CiaH variants and SCs, correspondingly divided by variants of ComX1, TrpE and CshA. StrH variants were associated with both SCs and invasiveness. Mentioned groups have eleven highly conservative membrane proteins with unknown function and possibly high vaccine potential.
Pathways of fatty acid synthesis are involved in virulence regulation. A number of known vaccine targets are confirmed and novel ones (surface and membrane proteins with unknown function) are proposed.