Genome analysis of a MDR Streptococcus pneumoniae 23F serotype causing meningoencephalitis in a 10-months refugee infant

Abstract

Purpose: Streptococcus pneumoniae is an important human pathogen causing invasive pneumococcal diseases (IPD). The re-emergence of eradicated S. pneumoniae-associated meningoencephalitis in Lebanon is a major point of concern. Methods: We aimed at conducting a comparative genome analysis of a multi-drug resistant S. pneumoniae, LAU-23F, linked to meningoencephalitis and fatality in a 10-months Syrian refugee infant in Lebanon, and 24 related publically available genome sequences. Serotype, capsular genes, MLST, SNPs, phylogenetic relatedness and repertoire of resistance genes were investigated. Genes encoding penicillin binding proteins (PBPs) were examined for mosaicity. Virulence factors were screened for SNPs as compared to reference strains. Results: The isolate belonged to ST-277 and was of serotype 23F. It showed an intermediate resistance to ciprofloxacin, cefuroxime and penicillin and carried multiple components of different efflux pumps. Gene mosaicity was observed in pbp2x, it was also distinct from other penicillin-resistant strains; pbp1a and pbp2b appeared to be conserved between LAU-23F and the reference strain SP49. The arrangement of capsular gene loci was similar to ATCC 700669 though polymorphism was detected in the cpsABCD region, believed to be conserved among different Streptococcus species. Amplitude of virulence factors was detected showing varying degrees of conservation compared to reference strains. Observed zones of high heterogeneity were associated with phage encoded regions. Conclusions: The fine levels of diversity throughout the genome could account for the pronounced invasiveness of this isolate. The genomicsbased methods used support the importance of implementing WGS in routine clinical diagnostics and surveillance of streptococcal diseases.