Research Abstracts Online
January 2010 - March 2011
University of Minnesota Twin Cities
College of Veterinary Medicine
of Veterinary Biomedical Sciences
PI: Connie J. Gebhart
Proliferative enteropathy is an important infectious disease caused by the obligate intracellular bacterium, Lawsonia intracellularis. The disease is well-established in pigs and has recently emerged in horses. There are at least two molecular subtypes of L. intracellularis, corresponding to the host source. Little is known about the molecular pathogenesis of this disease. The overall goals of this project are to comprehend the pathogenesis of Lawsonia infection, in vitro and in vivo, based on the evaluation of gene expression from host and pathogen, and to evaluate the development and intensity of lesions in pigs, horses and rodents, through cross-species experimental infection.
Preliminary data suggests that the ability of Lawsonia to cause disease is passage dependent. Lawsonia loses virulence upon cell culture passage (i.e., modified live vaccine), but researchers do not know a) the passage where virulence begins to decrease or totally ceases or b) what genes are involved in this loss of virulence. Therefore, these researchers are evaluating the effect of cell passage on Lawsonia virulence and determining at which passage it loses virulence completely. They also plan to use this information to identify genes involved in Lawsonia virulence. These low (virulent) and high (nonvirulent) passaged Lawsonia will be used to identify genes expressed during both in vivo and in vitro infection. Further, expression of virulent and nonvirulent Lawsonia will be compared using expression arrays or whole transcriptomes of the bacteria.
Virulent Lawsonia infection induces proliferation of infected enterocytes in vivo. Proliferation of commonly used cells (mouse, human, rat) has not been demonstrated in vitro. The researchers plan to determine the mechanism of proliferation by evaluating the gene expression profiles over time (chronologically) of cells infected with Lawsonia both in vitro (IPEC pig small intestine cells) and in vivo (live pigs and horses).
Molly Kelley, Graduate Student
Fabio Vannucci, Graduate Student