Genomic Approach to Understanding Infectious Disease Mechanisms

Close to 100 genomes of bacterial pathogens have been sequenced, and yet most of the genomes sequenced have approx 25% of their open reading frames annotated as proteins with no known function. When genomic sequences of virulent and nonvirulent strains of a particular species are available, comparative genomic analysis is a powerful tool to identify putative virulence genes. Variation in virulence between strains of the same species is a common phenomenon. Availability of the genome sequence of a pathogen permits the application of DNA microarrays to investigate the genetic basis of this variation. DNA microarray technology has facilitated the identification of putative virulence determinants, host specificity genes, and bacterial and host genes that are activated or repressed during an infection. Isogenic mutants and suitable virulence assays are critical in verifying the role of the putative virulence genes identified.