WHOLE GENOME SEQUENCE ANALYSIS OF S. PNEUMONIAE 12F ST-3774 - A LEADING CAUSE OF INVASIVE PNEUMOCOCCAL DISEASE ENDEMIC TO ISRAEL

Streptococcus pneumoniae is a global cause of invasive community acquired meningitis, sepsis and pneumoniae. S. pneumoniae serotype 12F is a non-prevenar serotype that has been a leading cause of invasive pneumococcal disease in Israel since 2009. Serotype 12F sequence types ST-218, ST-989 have been implicated in outbreaks globally. In Israel, a unique sequence type (ST-3774) accounts for 90% of 12F IPD. The clone is penicillin non-susceptible and susceptible to other commonly prescribed antibiotics. Though detected as a cause of IPD since 2000, the clone was rarely isolated before its emergence in 2009. We applied WGS analysis in order to study the population structure and dynamics of S. pneumoniae 12F in Israel during the period 2000-2015.

Whole-genome deep sequencing was performed on 17 clinical 12F strains isolated during 2000-2015. Whole genome SNP analysis indicated clonality (‹ 50 SNPs) and accumulation of mutations within the ST-3774 clone during 15 years. An MLST single locus variant (ST-3524) was closely related to the dominant clone. The Israeli clone was genetically distant compared with other 12F globally circulating 12F clones (ST-218, ST-989). Penicillin non-susceptibility was observed in all of the strains (MIC=0.12 µg/ml). Mutations in various penicillin binding proteins (PBPs) were detected including PBP2x transpeptidase domain, STMK binding motif. Four putative genomic islands, containing several genes encoding virulence factors and mobile genetic elements, were identified in ST-3774 and ST-3524 clones.

S. pneumoniae serotype 12F, not included in PCV13, is currently the most prevalent invasive pneumococcal serotype in Israel. Our analysis indicates a conserved population and existence of the ST-3774 clone prior to vaccine introduction. Our results highlight S. pneumoniae 12F as a current public health challenge, and a future vaccination target.