Integrated study of group B streptococcus and human ureaplasmas : the paradigm shifts

Abstract

Group B streptococcus (GBS, S. agalactiae) and human ureaplasmas (U. parvumand U. urealyticum) are two clinically and phylogenetically related, potentialperinatal pathogens. Their relationships between genotypes and pathogenesis ofGBS and ureaplasma infection were still not well understood, one of the reason isthat both of them are still short of a very practical genotyping system. In the study,to solve the above problem we developed genotyping systems for the organisms (thesecond section). For human ureaplasmas, based on four genes/gene clusters (rRNAgene clusters, the elongation factor Tu genes, urease gene complexes and multiplebanded antigen genes), we designed many primer pairs suitable for developing species identification assays for the two newly established human ureaplasmaspecies (U. parvum and U. urealyticum). Further, based on the heterogeneity ofureaplasma multiple banded antigen gene (which contains species- and serovar-specific regions), we developed genotyping methods for each ureaplasma species.For GBS, based on three sets of molecular markers (capsular polysaccharidesynthesis gene clusters, surface protein antigen genes and mobile genetic elements),we developed a genotyping system. The primary evaluation of the genotypingsystems showed that the genotyping systems were practical alternative assays forthe conventional serotyping and they will be useful to further explore therelationships between genotypes and pathogenesis of GBS and ureaplasmainfection. In the study, we introduced novel data and tools into GBS and ureaplasmastudies especially from genomic- and bioinformatics-based molecular microbiology(the third section). For two newly established human ureaplasma species, based onthe U. parvum serovar-3 genome, and using the above four important genes/geneclusters, we exposed some interesting problems in the understanding of newureaplasma taxonomy especially in the post genomic era. For GBS, we studied thetwo published full genomes and exposed some new problems or possible future newresearch fields. In particular we found the two finished and one ongoing GBSgenomes were all non-typical and suggest that future genomic project had better have genetic population structure viewpoint. Finally, we suggested that integratedstudies of the two potential or conditional perinatal pathogens, from the viewpointof evolution, would provide a new understanding angle of the pathogenesis of thetwo organisms. Studies suggested that during coevolution, human ureaplasmas(especially U. parvum) became friendlier than their ancestors to their human host(by losing most of its virulence genes); however, GBS tried to increase its invasiveabilities (by getting more virulence genes) to fight against the human host attack.