Microbiology

Murphy successfully defends PhD thesis

Murphy Cake web

Caitlin Murphy successfully defended her PhD thesis, "The role of cyclic di-GMP in regulating type 3 fimbriae - a colonization factor of Klebsiella pneumoniae," on Monday, April 7, 2014. Murphy is pictured here with her mentor, Steven Clegg, PhD.

Klebsiella pneumoniae is a Gram negative, enteric bacterium that frequently causes disease in immunocompromised individuals. These types of infections are often associated with the presence of indwelling medical devices, which provide a site for the organism to attach and subsequently form a biofilm. A key component in K. pneumoniae biofilm formation in vitro is type 3 fimbriae.

To determine if type 3 fimbriae are important in biofilm-mediated infections as hypothesized, we used a mouse model in which a silicone tube is implanted into the bladder of mice, mimicking the effects of catheterization. Using this model we have been able to show that type 3 fimbriae are required for colonization and persistence.

Our early work has indicated that type 3 fimbriae are regulated at least in part by the intracellular levels of the secondary messenger molecule cyclic di- GMP. Adjacent to the mrk fimbrial genes is a two-gene operon containing the determinants we have named mrkH and mrkI. mrkH encodes a PilZ domain containing protein, which we have shown binds cyclic di-GMP. Using a transcriptional fusion we have shown that the mrk gene promoter is activated modestly in the presence of MrkH, but when MrkH and MrkI are both present the activity is increased 100-fold. This has lead to the hypothesis that MrkH and MrkI interact, which we have been able to demonstrate using copurification procedures. This interaction appears to occur in a cyclic di-GMP dependent manner with the resulting protein complex binding to the mrk promoter region and activating the expression of type 3 fimbriae.

ABOUT CAITLIN:

Caitlin was born and raised in New Jersey. Along with her older sister Meghan, she was raised by two wonderful parents, Ben and Mary Jane. While completing a degree in Microbiology at the University of Michigan in 2007, she worked in a clinical and molecular epidemiology lab, which gave her the chance to do bench research for the first time. Knowing that she would like to pursue a career in science but not having much idea of what that actually meant, Caitlin went to the University of Nevada, Las Vegas where she studied electron donors involved in primary production in hot springs over 73°C.

After receiving her Master’s degree in 2009 from UNLV, Caitlin headed back to the Midwest to pursue a PhD at The University of Iowa. During her time at Iowa, Caitlin has had the privilege of working in the lab of Steve Clegg on the pathogenesis and regulation of type 3 fimbriae in K. pneumoniae. She has had the opportunity to present her work at national and regional conferences and make contributions to a review article, book chapter, and original research publications. She has also seen an increase in her ability to crossword.

If all goes well and she completes her PhD, Caitlin will be moving to Omaha, NE, for a CPEP fellowship in Clinical and Public Health Microbiology at the University of Nebraska Medical Center.

Outside of the lab, Caitlin enjoys time with her dogs, paddle sports, sandwiches, and overanalyzing potential craft projects. Her one regret during her graduate career is the lack of an online or in print presence for the Core 3 News.