Application Of Comparative Genomics On Some Important Pathogens

Infectious disease, especially emerging disease, has been one of the major threats to human health. Fuelled by the accumulation of huge amount of genome sequences, comparative genomics on pathogens, which explore the relationship between genomic variations and pathogenicitiy by comparison of bacterial genome contents and structures, has promoted a revolution in infectious research.Based on our bioinformatics approaches for comparative genomics, some important pathogens, including Streptococcus suis which can infect human and swine, Staphylococcus epidermidis, the most frequent cause of nosocomial infections associated with implanted medical devices, and Saccharomyces cerevisiae strain YJM789, derived from yeast isolated from the lung of an AIDS patient with pneumonia, were studied.In order to study the pathogenicity mechanism of S. suis, we annotated and analyzed the genomes of two strains, S. suis P1/7 and 89-1591. 1306 homolog ORFs, including some toxicity factors, were identified between two strains. While 4 (cps 2A, 2B, 2I and 2J) genes encoding for the capsules only present in P1/7. In addition, Eight genomic islands were identified which may contribute to the pathogenecity of S. suis.A comparison of dN/dS value on orthologs with SNPs between S. epidermidis strain ATCC12228 and RP62A revealed that 40 ortholog gene pairs have a disproportionate distribution of dN vs dS, suggesting that they maybe involved in the pathogenecity process. Two main groups were observed in the cluster of 40 genes: surface proteins, which are likely under pressure to escape the host immune system, and other genes that should be considered in priority as important for pathogeicity. Among those, the presence of the gene encoding methionine sulfoxide reductase suggested a possible involvement of reactive oxygen species. This led us to uncover that the infection associated strain was significantly more resistant to hydrogen peroxide and paraquat than the environmental strain.The genome of S. cerevisiae strain YJM789 contains more than 59,000 single nucleotide polymorphisms and is more than 45 Kb indels in comparison with the S288c genome. Close examination of the highly polymorphic region on chromosome I, which encompasses five members of the nonessential DUP240 gene family encoding putative integral membrane proteins, showed that introgression with S. paradoxus may responsible for it. Another interesting diverged region is highly localized on PDR5, which encodes a multidrug transporter. In addition, multiple open reading frames in YJM789, including GNAT, encoding a GCN5 related N-acetyltransferase, were acquired by horizontal transfer from bacteria.The relationship of the genomic variations, including SNPs, insertion/deletions, with pathogenicity was explored in detail in those important pathogens. Our study proposed a novel approach for identifying of genes involved in pathogenic processes and provided some insight into the molecular mechanisms leading a commensal inhabitant to become an invasive pathogen. In addition, with the comprehensive genomics information for the important pathogens, our results shed insights for the further study in the molecular mechanism of pathogenecity, as well as disease prevention, vaccine development and drug design in the future.