Microbiology

Jennifer Walker successfully defends PhD thesis

Jennifer Walker Defense

Jennifer Walker successfully defended her PhD thesis, "The Two-Component System, ArlRS, Regulates Agglutination and Pathogenesis," on Thursday, June 20, 2013.  Walker is pictured here with her mentor, Alex Horswill, PhD.

Staphylococcus aureus is a Gram-positive bacterial pathogen that is defined by its ability to agglutinate in the presence of human plasma. Although agglutination has long correlated with disease severity, the function of the process remains unclear. Increasing evidence suggests the mechanisms of agglutination are highly complex and poorly understood.

To investigate the agglutination process, we developed both tube based and flow cytometry methods to quantify clumping in the presence of extracellular matrix proteins. The development of these assays allowed for the discovery of a novel regulator of clumping and pathogenesis, the two-component system, ArlRS. Characterization of the inhibitory effects arlRS mutants have on agglutination revealed ArlRS regulates agglutination through a unique mechanism that depends on the surface protein Ebh. The ebh gene, encoding the giant surface protein Ebh, is up-regulated in an arlRS mutant. Deletion of ebh in an arlRS mutant restores agglutination to wildtype levels, demonstrating that Ebh has a negative impact on the agglutination mechanism.

To assess the role of an arlRS mutant in pathogenesis, a rabbit combined model of sepsis and endocarditis was performed. In this model the arlRS mutant displayed a defect in vegetation formation and pathogenesis. Prior to this work, little was known about the function of ArlRS or the surface protein Ebh. We have demonstrated that the ArlRS system controls a novel mechanism through which S. aureus regulates agglutination and pathogenesis.

ABOUT JENNIFER:

Jen was born and raised in the St. Louis suburb of Webster Groves, MO. During her senior year at Webster Groves High School Jen participated in an internship in the lab of Scott Hultgren at Washington University in St. Louis, researching the binding pocket of the type 1 pilus adhesin in pathogenic E. coli. This opportunity was pivotal in instilling a love of science and the drive to do hypothesis-based research. Following high school graduation, Jen first attended Washington University in St. Louis and then University of Missouri-St. Louis, where she was able to continue her studies in the Hultgren lab. This work led to eight publications over the course of five years.

After graduation from the University of Missouri in 2008, Jen entered the PhD program in the Department of Microbiology in Fall 2008. She joined the Horswill Lab in Fall 2009 and began her studies on the ArlRS two-component system (TCS) in Staphylococcus aureus. As a graduate student, Jen has published one first author paper based on her work developing a new coverslip-based biofilm assay and has a second first author paper under revisions at PLOS Pathogens to be resubmitted soon. Jen was given the opportunity to present her work at several conferences, including the International Symposium on Staphylococci and Staphylococcal Infections in Lyon, France, and the International Conference on Gram Positive Pathogens, in Omaha, NE. She is fortunate to be supported by the American Heart Association Pre-doctoral Fellowship.

Outside of lab, Jen is an avid kayaker and spends the few warm days during Iowa summers out on Lake Macbride. She is also a wine enthusiast and enjoys the area’s variety of local wineries. She spends her time with her boyfriend Blake gardening and traveling.

After graduation she will be moving to St. Louis to begin a postdoctoral position at Washington University in St. Louis. She is excited to be moving back to St. Louis for a brief time.