DNA Microarray Analysis of Host Pathogen Interaction

Understanding the molecular basis of the host response to bacterial infections is critical for understanding disease mechanisms involved, and in preventing disease and tissue damage resulting from the host response. The global transcription effects on host cells by various bacterial pathogens including Listeria monocytogenes, Salmonella typhimurium, Pseudomonas aeruginosa, Bordetellapertussis,Mycobacterium tuberculosis, H. pylori, and Chlamydia trachomatis have been analyzed by using microarray technology (29,30). Rosenberger et al. (31) identified novel macrophage genes whose level of expression are altered in S. typhimurium infection or when treated with lipo-polysaccharide. Similarly, Cohen et al. (32) identified 74 upregulated RNAs and 23 downregulated host RNAs in L. monocytogenes-infected human promyelocytic THP1 cells. Infection of human bronchial epithelial cells by B. pertussis results in an increase in transcriptional levels of 33 genes and decrease in transcriptional levels of 65 genes (33). Many of the upregulated genes encode proinflammatory cytokines (e.g., inter-leukin-8, interleukin-6, and growth-related oncogene-1) and many of the downregu-lated genes encode transcriptional factors and cellular adhesion molecules.

H. pylori is a human gastric pathogen that causes gastritis, gastric ulcer, and duodenal ulcer, and is implicated to enhance the incidence of mucosa-associated lymphoid tissue lymphoma and gastric cancer. The genomes of H. pylori strains sequenced contain a pathogenicity island (PAI) denoted cag (cagPAI), which has been shown to be a major virulence factor encoding about 30 proteins (34; Chapter 6). The cagPAI encodes a type IV secretion system that facilitates transfer of virulence factors to the host cells (35). Nagasako et al. (36) used cDNA microarrays to compare the effects of cagPAI-positive and cagPAI-negative H. pylori in altering the gene expression of infected gastric epithelial cells. This study showed that a host protein, Smad5, was upregulated in cagPAI-positive H. pylori-infected cells, but not the cagPAI-negative cells. The upregulated expression of Smad5 mRNA is required for induction of apoptosis of gastric epithelial cells because inhibition of Smad5 mRNA expression by Smad5-specific siRNA prevents apoptosis (36).

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