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Comparative Genomics

As a group of organisms, the streptococci have both common themes and differences which emphasize their individuality and genetic diversity. The availability of several genome sequences within a given species illustrates that significant differences occur even in the same serotype. Horizontal gene transfer and recombination, common to all the streptococci, has contributed greatly to the generation of strategies for the survival of an organism in its ecological niche. These strategies include altering or deleting surface structure genes to evade the host immune system, gaining new genes such as surface proteins with particular binding affinities, gaining or deleting metabolic pathways for suitable nutrient acquisition, and addition of new virulence genes such as exoenzymes and toxins. Prime examples are the bacteriophage transfer of superantigen genes to new GAS hosts and the highly efficient transformation system of S. pneumoniae, generating mosaic structures, genomic rearrangements, and genetic diversity. In both cases new clones with increased virulence properties are created which have the ability to eventually disseminate a new wave of disease.

The ecological niche and the environment of an organism is reflected in the genetic makeup of pathways and other fitness traits essential for its existence. Organisms such as the GAS in the pyogenic group live in a nutrient-rich environment [76] and cannot survive without substrates available from host tissues. Their metabolic pathways mirror this need with virtually no pathways present for the synthesis of amino acids, but at the same time possessing several ABC transporters for amino acid uptake systems, as well as additional transporter systems for the uptake of dipeptides and oligopeptides. In contrast, organisms such as the mitis group of streptococci contain additional pathways essential for an environment not so rich in nutrients where different kinds of substrates are present. These include additional and different uptake and transport systems as well as different regulatory controls. One member of the mitis group, S. pneumoniae, has a high proportion of sugar transporter genes, a feature that allows it to compete for sugars with other respiratory tract bacteria. Gene expression profiling under various environmental conditions will be an important avenue for future investigation.

Evolutionary changes in genomes can be illustrated by aligning orthologous regions of sequences. Large-scale changes such as rearrangements may result in regions of one genome being inverted or reordered relative to another. Figure 8.1 illustrates how closely related organisms of the same species are generally closely aligned, with a high conservation of gene order and orientation. Inversions and rearrangements in these genomes is equally obvious, indicating more recent changes. Such a change led Nakagawa et al. to suggest that clonal expansion of the rearranged M3 strains may be related to recent increases in rheumatic fever and severe invasive infections in Japan [7]. The lack of alignment of genomes from different streptococcal species illustrates that larger changes have occurred with little concordance of gene block sequence and order, and suggests that these genomes are constantly undergoing rearrangements (not shown).

The genomes of the streptococci are proving to be powerful tools in the understanding of how these organisms gain new virulence genes as well as discovering new approaches to combating their pathogenic potential. Postgenomic approaches such as microarrays, proteomics, and structure-function studies will fill in many of the gaps remaining in our understanding of these organisms, particularly in identifying ORFs with unknown function, new putative virulence genes, and regulatory networks controlling gene expression. Clearly, important work remains to be completed for rational drug development aimed at newly identified target genes as well as the identification of new antigens for vaccines.

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