Emerging Infectious Diseases

The complex interaction between a microbial pathogen and a host is the underlying basis of infectious disease. By understanding the molecular details of this interaction, we can identify virulence-associated microbial genes and hostdefense strategies and characterize the cues to which they respond and mechanisms by which they are regulated. This information will guide the design of a new generation of medical tools. Genomic sequencing will provide the data needed to unravel the complexities of the hostpathogen interaction. As of August 10, 2000, draft sequence was available for 87% of the human genome (http://www.ncbi.nlm.nih.gov/genome/ seq/), and at least 39 prokaryotic genomes, including those of more than a dozen human pathogens, had been completely sequenced (http://www.tigr.org/tdb/mdb/mdbcomplete.html). The pace of gene discovery rapidly accelerates, but its potential for explaining life at the molecular level remains largely unrealized because our understanding of gene function lags increasingly far behind. For example, even in the heavily studied Escherichia coli, no function has been assigned to more than one third of its genes (1). High-throughput methods for assessment of function are clearly required if this wealth of primary sequence information is to be used. Global profiling of gene expression is one attractive approach to assessing function. Because a gene is usually transcribed only when and where its function is required, determining the locations and conditions under which a gene is expressed allows inferences about its function. Several independent high-throughput methods for differential gene expression (including SAGE and differential display) may enable function annotation of sequenced genomes (2). DNA microarray hybridization analysis stands out for its simplicity, comprehensiveness, data consistency, and high throughput. Transcription control plays a key role in hostpathogen interaction (3,4); thus, genomewide transcription profiling seems particularly appropriate for the study of this process. This review focuses on microarray-based approaches for studying transcription response because they hold exceptional promise for the study of infectious disease. Microarray-based genotyping applications, although expected to make substantial contributions in this field, are covered only briefly here. Using DNA Microarrays to Study Host-Microbe Interactions