Professor and Department Chair - Veterinary and Biomedical Sciences

e-mail: isaac015@umn.edu

Research Interests
My laboratory is studying the molecular basis of pathogenesis of two pathogens: Escherichia coli and Salmonella typhimurium. 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. Our 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), hilA, invH, and sigD. The over expression of lrhA increases the rate of phase variation from the non-adhesive to the adhesive phenotype. Our 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 are absent in non-pathogenic strains, but are present in strains that cause urinary tract infections and sepsis. Mutations in these genes results in attenuation of the E. coli strain in vivo. One gene system has been characterized as a novel iron transport system, term Fit. In a third project, we are studying microbial population shifts in the intestines of pigs in response to treatment with an antimicrobial growth promoter, if there are shifts in the carriage and load of food borne pathogens in these animals, and health status of these animals.

Selected Publications
(For a comprehensive list of  Dr. Isaacson's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Khan, M, A., and Isaacson, R.E. Identification of Escherichia coli genes that are specifically expressed in a murine model of septicemic infection. Infection and Immunity 70:3404, 2002.

Isaacson, R.E. Genomics and the prospects for the discovery of new targets for antibacterial and antifungal agents. Current Pharmaceutical Design 8:1091, 2002.

Barber, D.A, Bahnson, P.B., Isaacson, R.E., Jones, C.J., and Weigel, R.M. Distribution of Salmonella in swine production ecosystems. J. Food Protect. 65:1861-1868 (2002).

Correa-Matos, N.J, Donovan, S.M, Isaacson, R.E., Gaskins, H.R., White, B.A., and Tappenden, K.A. Fermentable Fiber Reduces Recovery Time and Improves Intestinal Function in Piglets Following Salmonella typhimurium Infection, J. Nutrition 133:1845-1852 (2003).

Isaacson, R.E. MBI-266 Micrologix/Fujisawa. Curr. Opin.Invest. Drugs 4:999-1003 (2003).

Althouse, C., Patterson, S.K., Fedorka-Cray, P., and Isaacson, R.E. Type 1 fimbriae of Salmonella enterica serovar Typhimurium bind to enterocytes and contribute to colonization of swine in vivo. Infect. Immun. 71:6446-6452 (2003).

Weigel, R. M., Qiao, B., Terferedegne, B., Suh, D. K., Barger, D. A., Isaacson, R. E., White, B. A. Comparison of pulsed field gel electrophoresis and repetitive sequence polymerase chain reaction as genotyping methods for detection of genetic diversity and inferring transmission of Salmonella. Veterinary Microbiology, 100:205 (2004).

Singer, R. S., Cooke, C. L., Maddox, C. W., Isaacson, R. E., Wallace, R. L.  Use of pooled samples for the detection of Salmonella in feces by polymerase chain reaction. J. Veterinary Diagnostic Investigations 18:319 (2006).

Ouyang, Z. and Isaacson, R. E. Identification and characterization of a novel ABC iron transport system, fit in Escherichia coli. Infection and Immunity 74:6949 (2006).

Bahnson, P.B., Damman, D.J., Isaacson, R.E., Miller, G.Y., Weigel, R. M., and Troutt, H.R. Prevalence and serovars of Salmonella enterica isolated from ileocolic lymph nodes of market pigs reared in selected midwest US swine herds. Journal of Swine Health and Production, 14:182 (2006).

Weigel, R. M,. Nuvera, D., Qiao, B., Teferedegne, B., Suh, D. K., Barber, D. A., Bahnson, P. B., Isaacson, R. E., White, Bryan A. Testing an ecological model for transmission of Salmonella enterica in swine production ecosystems using genotyping data. Preventive Veterinary Medicine xx:xxxx (2007).

Current Funding
USDA. NRICGP. Quantitative measurement of antimicrobial resistance gene loads in samples, 2004-2007, CoPI.

USDA, NRICGP. Food safety research and response network (FSRRN). 2005-2008, CoPI.

USDA, NRICGP. Potential public health and food safety impacts associated with used of antibiotic growth promoters, 2007-2010, PI.

Honors and Awards
Fellow in the American Academy of Microbiology, 1988.

Phi Zeta Veterinary Honor Society Honorary Member, 1994.

Pfizer Award for Research Excellence, 1998.

Vice President, Conference of Research Workers in Animal Diseases, 2006-2007.

President, Conference of Research Workers in Animal Diseases, 2007-2008.

Current Students