Research
Topics Department of Veterinary Pathobiology
Ph.D. (1974) University of Illinois
Research
Topics
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Attachment of Escherichia coli to Mucosal Receptors
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Regulation of Adhesions
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Persistence of Salmonella in Animals
Research
Interests
My laboratory is studying the molecular basis of pathogenesis of two enteric pathogens (enterotoxigenic Escherichia coli and Salmonella typhimurium) and the mechanisms involved in E. coli nosocomial septicemia. A common theme in each project is the identification of unique genes required for pathogenesis, understanding the functions of those genes, and determining the mechanisms controlling their expression. Adhesion of enterotoxigenic E. coli to mucosal surfaces is an essential process in disease and is mediated by pili. We have been studying two pilus-adhesins: K99 and 987P. Using various genetic techniques we were able to show that the 8 K99 genes are divided into 3 separately regulated operons. Currently, efforts are underway to understand how expression of the 3 operons is coordinated with the end result the production of K99. In the 987P system, we are trying to unravel the mechanism controlling another genetic regulatory phenomenon called phase variation. This process allows cells to grow such that they either produce 987P or they do not. The phases are meta-stable and can switch back and forth.
Studies on S. typhimurium are directed toward an understanding of the mechanism whereby S. typhimurium can persistently infect pigs, yet not cause. We have isolated two phenotypic variants believed to be phase variants, one of which can attach to porcine villous epithelial cells and the other cannot. Mutations were selected in the adhesin genes and the adhesin shown to be type 1 fimbriae. Non-adhesive mutants exhibited decreased virulence in mice and failed to colonize the intestines of pigs. Through gene cloning, several additional genes co-regulated with type 1 fimbriae were identified including rfaL (O-antigen ligase), pefB, hilA, invH, and sigD.
Work on E. coli nosocomial septicemia has employed in vivo gene expression technology to identify genes exclusively expressed during disease. Approximately 300 clones have been sequenced to determine the nature of some of these genes. In the collection of identified genes are 7 sequences that have no sequence homology to any E. coli sequences and represent a set of previously unknown genes.
Key Words
Recombinant DNA, DNA-Protein Interaction, Protein-Protein Interaction, Genome Organization/RFLP Mapping, Disease Models, Host/Parasite Interactions
Current
Research Funding USDA/NRI, Johnson and Johnson