Richard Isaacson

 e-mail: isaac015@umn.edu
 

My laboratory is studying the molecular basis of pathogenesis of two pathogens: Escherichia coli and Salmonella enterica serovar 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. enterica serovar Typhimurium are directed toward an understanding of the mechanism whereby S. enterica serovar 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. To date we have found distinct population shifts earlier in the growth of pigs in response to Tylosin but there were no differences in health status. Finally, we are assessing the microbiota in the lungs of patients who have had lung transplants. These patients have a greater diversity of microbes compared to non-transplant patients.

Selected Publications

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

Kim, H.B., Borewicz, K., White, B.A., Singer, R.S., Sreevatsan, S., Tu, Z, J., Isaacson, R.E. Longitudinal investigation of the age-related bacterial diversity in the feces of commercial pigs. Veterinary Microbiology (2011) doi:10.1016/j.vetmic.2011.05.021.

Danzeisen, J. L., Kim, H. B., Isaacson, R. E., Tu, Z. J., Johnson, T. J. Modulations of the Chicken Cecal Microbiome and Metagenome in Response to Anticoccidial and Growth Promoter Treatment. PLOS One, 6: 1-14 (2011).

Shepard, S., Danzeisen, J., Isaacson, R., Seemann, T., Achtman, M., and Johnson, T. Genome Sequences and Phylogenetic Analysis of K88- and F18-Positive Porcine Enterotoxigenic Escherichia coli. J. Bacteriology, 194:395-405 (2012).

Isaacson, R. and Kim, H. B. The intestinal microbiome of the pig. Animal Health Research Reviews 13:100-109 (2012).

Patterson, S. K, Borewicz, K., Johnson, T. Xu, W., and Isaacson, R. E. Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium. PLoS One, 11: e43592( 2012).

Kim , H.B., Borewicz ,K., White, B.A, Singer, R.S., Sreevatsan, S., Tu, Z. J., and Isaacson, R. E. Microbial shifts in the swine distal gut in response to the treatment with antimicrobial growth promoter, tylosin. PNAS 109: 15485 (2012).

Pragman, A.A., Kim, H.B., Reilly, C.S., Wendt, C., and Isaacson, R.E. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One, 7(10): e47305 (2012).

Borewicz, K., Prgaman, A. A., Kim, H.B., Hertz, M., Wendt, C., and Isaacson, R.E. Longitudinal analysis of the lung microbiome in lung transplantation. FEMS Microbiology Letters, 2012 Nov 22. doi: 10.1111/1574-6968.12053.

Current Funding

Minnesota Agricultural Experiment Station, The mechanism mediating long term colonization of pigs by Salmonelle enterica, 1/13-12/14, PI.

Department of Homeland Security, Cultivation and detection of Francisella and Yersinia, 2010-2013, CoPI.

Current Students
 

Alexa Prgaman