Mosaic genes and mosaic chromosomes: Intra- and interspecies genomic variation of Streptococcus pneumoniae

Streptococcus pneumoniae remains a major causative agent of serious human d iseases. The worldwide increase of antibiotic resistant strains revealed th e importance of horizontal gene transfer in this pathogen, a scenario that results in the modulation of the species-specific gene pool. We investigate d genomic variation in 20 S. pneumoniae isolates representing major antibio tic-resistant clones and 10 different capsular serotypes. Variation was sco red as decreased hybridization signals visualized on a high-density oligonu cleotide array representing 1,968 genes of the type 4 reference strain KNR. 7/87. Up to 10% of the genes appeared altered between individual isolates a nd the reference strain; variability within clones was below 2.1%. Ten gene clusters covering 160 kb account for half of the variable genes. Most of t hem are associated with transposases and are assumed to be part of a flexib le gene pool within the bacterial population; other variable loci include m osaic genes encoding antibiotic resistance determinants and gene clusters r elated to bacteriocin production. Genomic comparison between S. pneumoniae and commensal Streptococcus mitis and Streptococcus oralis strains indicate s distinct antigenic profiles and suggests a smooth transition between thes e species, supporting the validity of the microarray system as an epidemiol ogical and diagnostic tool.