Mitis Group Streptococcus pneumoniae

The most notable member of the mitis group is Streptococcus pneumoniae, which is found primarily in the nasopharynx. It is responsible for a great deal of human disease, including acute bacterial pneumonia and invasive disease. It contains no Lancefield group-specific antigens and is subdivided into more than 90 groups based on polysaccharide capsule type. Two genomes of S. pneumoniae have been completely sequenced, and a third is in progress (Tables 8.1, 8.2). Additionally, a sequence diversity study of 14 different strains with important phenotypic and pathogenetic differences is in progress ( info/).

The two S. pneumoniae sequenced strains have a genome size and G+C content of 2.03 Mbp and 40% respectively for the type 2 capsule R6 strain, [57] and 2.16 Mbp and 39.7% for the type 4 capsule TIGR4 strain [58]. With an almost 10% difference in gene content between the two strains, there are strain-specific multiple gene clusters present in each genome. Several of these clusters contain genes encoding cell surface proteins known to interact with host cells and which appear to have sequence variability. S. pneumoniae has been appropriately termed a "paradigm for recombination-mediated genetic plasticity" [59], because of its natural competence and high transformability. The S. pneumoniae genome contains numerous IS, BOX, and RUP repetitive elements which account for up to 5% of the genome and represent hotspots for genetic recombination. More than 250 duplicated genes are present in the genome as well as nearly 400 genes with iterative motifs that can result in phase variation. Additionally, codon preference profiles of almost 500 genes in S. pneumoniae showed a lower G+C content (33.4%) than in most of the genome (39.7%), suggesting that they were obtained by horizontal gene transfer [60]. Some of these genes may have come from other organisms since Tettelin et al. identified at least 40 genes with significant homology to genes in gram-negative bacteria [58]. Evidence of intragenic recombinations creating mosaic structure is apparent in several genes, including the penicillin binding proteins, which contained segments identical to genes of other streptococcal species [61]. Genome heterogeneity, mosaic genes, and plasticity are features not only of S. pneumoniae, but are also found in other members of the mitis group of streptococci [62]. Streptococcus mitis, Streptococcus sanguis, and Streptococcus gordonii

Further members of the mitis group of streptococci, but which also possess the Lancefield group H antigen, are Streptococcus mitis, Streptococcus sanguis, and Streptococcus gordonii. These species predominate in the oral cavity, and the sequencing of each of the genomes is in progress (Table 8.2). While generally considered human commensals, these organisms may play important roles in dental or medical disease. One series of studies found that S. mitis released superanti-gen-like molecules that might promote the oral inflammatory response [63]. Subsequently, at least one outbreak of streptococcal toxic shock syndrome was reported with S. mitis as the causative agent, validating the earlier observations [64]. Pneumolysin, a major virulence factor in S. pneumoniae, is also present in S. mitis [65], suggesting that horizontal transfer occurs between these species.

S. mitis is an occasional cause of infective endocarditis, and bacterial binding of platelets is an important mechanism in the pathogenesis of this disease. Platelet binding by S. mitis is mediated by the surface proteins PblA and PblB, encoded by a lysogenic bacteriophage [66, 67]. Thus, it is possible that S. mitis shares a number of genetic characteristics with the better known pathogenic streptococci, and the analysis of the genome of this organism may reveal even further insights into potential virulence mechanisms. No similar association between a temperate phage and the transmission of virulence traits has been seen yet in S. sanguis or S. gordonii.

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