Olivia Chuang

E-mail: chua0041@umn.edu

Thesis Advisor: Gary Dunny

Year entered: 2003

Degrees received:
B.A., Biology, Washington University, St. Louis, MO, 2002

Honors and Awards:

• Minnesota Craniofacial Research Training Grant (MinnCResT) 2004-2008

Thesis research:
Enterococcus faecalis has become an increasingly serious issue in nosocomial environments, implicated as an etiological agent in endocarditis, bacteremia and urinary tract infections.  Transfer of antibiotic resistance genes through conjugation has contributed to the spread of resistant strains.  Conjugation is first mediated by the expression of aggregation substance (Asc10), which induces binding between a donor and recipient cell.  Asc10 is a 137-kDa surface protein encoded by the prgB gene on the pheromone-induced conjugative plasmid pCF10, involved in plasmid transfer as well as in mediating attachment to host tissues.  Several domains have been identified in Asc10, including two aggregation domains, two RGD motifs, and a C-terminal domain.  Studies have shown that Asc10 expression increases the size of vegetations in a rabbit endocarditis model, in addition to promoting internalization of Asc10-expressing E. faecalis by intestinal epithelial cells and phagocytes.  This project intends to investigate the role of Asc10 in host tissue interactions, specifically its involvement in promoting E. faecalis interactions with tissue such as heart valves in the endocarditis disease model.  Techniques to be employed include the use of a rabbit endocarditis catheter model, a porcine valve tissue adherence model, and a DNA microarray chip analysis to characterize the host response to Asc10-expressing E. faecalis.  Also, molecular cloning techniques will be employed to design more Asc10 mutants, in order to characterize domains that are involved in these host tissue interactions.  Use of a macrophage or neutrophil cell line will investigate how Asc10 is able to increase the ability of E. faecalis to survive intracellularly, as well as possibly interfere with phagosomal maturation.

Publications:

• Chuang, O. N., P. M. Schlievert, C. L. Wells, D. A. Manias, T. J. Tripp, and G. M. Dunny. Multiple functional domains of Enterococcus faecalis aggregation substance Asc10 contribute to endocarditis virulence. Submitted to Infection and Immunity.
• P. M. Schlievert, O. N. Chuang, M. L. Peterson, S. M. Grindle, L. C. Case, and G. M. Dunny. Reduction of Enterococcus faecalis endocarditis with IgG fab fragments that interfere with aggregation substance-mediated immune response suppression. Submitted to Journal of Immunology.