Molecular characteristics of penicillin-binding protein genes of penicillin-nonsusceptible Streptococcus pneumoniae isolated in the Netherlands

Recently, a nation-wide molecular epidemiologic survey of penicillin-nonsusceptible Streptococcus pneumoniae has been performed in the Netherlands. In the current study, we analyzed the genes pbpla, pbp2b, and pbp2x from these clinical isolates at the molecular level, and identified the genetic composition of the penicillin-binding domains. The pneumococcal strains were selected on the basis of differences in restriction fragment length polymorphism (RFLP) patterns of the genes pbpla, pbp2b, and pbp2x, and represented 8, 7, and 10 distinct patterns, respectively. The genetic heterogeneity observed by sequence analysis of the pbp gene parts was comparable with the heterogeneity of the entire pbp genes as deduced from RFLP analysis. Furthermore, the mutations in the pbp sequences of the Dutch isolates invariably matched with the mutations described in pbp sequences of penicillin-nonsusceptible pneumococci isolated in other countries. Finally, novel mosaic structures were identified indicating horizontal exchange of pbp gene parts among penicillin-nonsusceptible pneumococci.