Alexandra E. Paharik defends Phd Thesis

Tuesday, June 28, 2016

On June 23, 2016, Alexandra Paharik successfully defended her thesis titled, "Novel roles of staphylococcal proteases and cross talk in biofilm formation and virulence”.  She is pictured with her mentor Dr. Alexander Horswill.

The staphylococci are a diverse genus of nearly 50 species of Gram-positive bacteria that colonize humans and other mammals. Although typically benign, some staphylococcal species are also opportunistic pathogens, particularly S. epidermidis and S. aureus. These organisms are responsible for a large portion of bacterial infections in humans. My thesis work has focused on studying how staphylococcal secreted proteases contribute to infection. I also investigated communication between different staphylococcal species, or “cross talk.”

S. epidermidis infections typically occur on implanted medical devices, such as artificial joints. These infections are characterized by the formation of a biofilm, which is a community of bacteria that is adherent to a surface and encased within a sticky matrix. Biofilm infections are difficult to eradicate by conventional antibiotic treatment. S. epidermidis biofilm formation requires an adhesive protein called Aap that promotes intercellular attachment once it is cleaved by a protease. We found that the S. epidermidis metalloprotease SepA is required for Aap-mediated biofilm formation, and that it cleaves Aap at two residues. The S. aureus homolog of SepA also promotes Aap-mediated biofilm formation in S. epidermidis.

In another project, we investigated the ability of S. caprae to inhibit quorum sensing in S. aureus. All staphylococci possess quorum sensing, which is a mechanism to detect their population density and coordinate group behavior. We found that the animal-associated species S. caprae produces a factor that disrupts quorum sensing in S. aureus. We identified this factor and showed that it inhibits the progression of a S. aureus murine skin infection.

Biographical Sketch

Allie grew up in Greensburg, Pennsylvania with two brothers, Ethan and Jimmy, and one sister, Bayley. She thanks her siblings for being her earliest experimental subjects while she tested things like the best way to give a haircut or extract someone’s loose tooth. College provided more opportunities for scientific discovery, and Allie got her first taste of research studying the mitotic spindle assembly complex in an advanced cell biology course under the direction of Dr. Kevin Vaughan.

 After taking microbiology, she became curious about studying pathogenic bacteria, and did three semesters of undergraduate research with Dr. Jeffrey Schorey. Her project focused on the role of exosomes in the macrophage response to mycobacteria. Working in the lab quickly became her favorite way to spend time (other than cheering on the Fighting Irish at football games), and with the guidance of Dr. Schorey, Allie decided to apply to graduate schools to pursue her Ph.D. She was thrilled to have the opportunity to come to the University of Iowa, and considers herself an honorary Midwesterner after her time here. Her first rotation was in Dr. Alex Horswill’s lab characterizing two component system mutants of S. aureus. After her undergraduate research on the notoriously slow-growing mycobacteria, she was excited to work on Staph and never looked back. She joined Alex’s lab in the Spring of 2011. Her research during graduate school has led to one first author paper that is submitted and two others in preparation. She also has written a book chapter and is a contributing author on four other papers. She has been fortunate to present at several conferences, most recently ASM Biofilms, at which her S. epidermidis biofilm project was selected for a talk. After completing her research at the end of the summer, she hopes to begin a postdoctoral position studying host interactions with bacteria.

When not in the lab, Allie can be found testing new baking recipes, cheering on her favorite sports teams (which now include the Iowa Hawkeyes), or attempting to become a faster runner.