Application of Microarray Analysis to the Investigation of Host-Pathogen Interactions

Abstract

Researchers have traditionally identified pathogenesis-related bacterial genes using molecular fingerprinting techniques such as restriction fragment length polymorphisms (RFLP) and random arbitrarily primed PCR (RAP PCR) to compare virulent and avirulent isolates. A more comprehensive approach to understanding the different pathogenic effects of diverse bacteria on their hosts requires that each gene within the bacterial genome be interrogated simultaneously. The availability of 95 complete genome sequences from 83 different microbial species and the development of microarrays containing representations of genes for many of these pathogens provide both of the prerequisites required for this approach. Helicobacter pylori induces gastric inflammation in all hosts, and such gastritis increases the risk for peptic ulceration, distal gastric adenocarcinoma, and gastric mucosal lymphoproliferative disease. H. pylori have now been completely sequenced, and genomic comparison has revealed that between 6 and 7% of the genes are strain-specific, reflecting a high level of genetic diversity. Contact between a host and a specific microbial pathogen not only alters bacterial gene expression but also results in dramatic changes in eukaryotic gene expression. Experiments involving exposure of bacteria to conditions that are similar to those encountered in vivo followed by assessment of the transcriptional responses using microarrays will undoubtedly become more common as investigators continue to elucidate bacterial signaling pathways that are involved in pathogenic host-microbial interactions.