Emerging Infectious Diseases

Twenty-five years ago, the development of molecular biology and recombinant DNA technology promised breakthroughs in infectious disease research. Since then, these methods have slowly teased out molecular secrets of microbial infection, gene by gene. Now, with the advent of whole-genome sequencing, a new revolution in infectious disease research has begun. Genomics is a top-down approach to the study of genes and their functions, taking advantage of DNA sequences of complete genomes. Determining the DNA sequence of a complete genome is a major activity of genomics. Although basic DNAsequencing methods have remained the same, advances in automation and informatics enable determination of whole microbial genome sequences in <2 years. Complete knowledge of an organism’s genetic makeup allows exhaustive identification of candidates for virulence genes, vaccine and antimicrobial targets, and diagnostics. The genomes of at least 13 pathogenic bacteria have been sequenced (Table 1), representing >20,000 putative genes. The genomes of at least 28 other pathogenic bacteria are being sequenced, promising >40,000 additional genes. This tally does not include an equally large number of nonpathogenic bacteria undergoing whole-genome sequence analysis. These new data dwarf previous methods of gene discovery, allowing many new genetic approaches to understanding pathogenesis.