Student: Shailagne Yutuc
Project: Inhibition of Leukotoxin Activity Through Receptor-Based Peptides | View Poster (PDF)
Institution: Lehigh University
Major: Chemical and Biomolecular Engineering
Advisor: Angela Brown
Abstract
The leukotoxin (LtxA) is secreted by the bacterium Aggregatibacter actinomycetemcomitans and is a member of the RTX (repeats-in-toxin) family. This toxin has been described as a “key” virulence regulator of the bacterium, as it specifically kills white blood cells, thus inhibiting the immune response to the infection. In its initial interaction with the host white blood cell membrane, the toxin must either bind to an integrin receptor, lymphocyte function-associated antigen-1 (LFA-1) and cholesterol. The goal of this project was to investigate the inhibition of (1) LtxA-LFA-1 and (2) LtxA-Cholesterol binding through the use of small peptides to block LtxA from binding to its binding sites. To inhibit LtxA-LFA-1 binding, we synthesized peptides based on the sequence of the LtxA binding sites in LFA-1 and measured their ability to block LtxA activity. We found that several of the peptides, specifically those that corresponded to the sequential β-strands in the β-propeller domain of LFA-1, inhibited the cytotoxicity of LtxA. We also found that there was a correlation between peptide-LtxA affinity and toxin activity. Our data revealed that the peptide and toxin bind to each other, leading to a decrease in LtxA binding to the LFA-1 receptor. We also investigated whether blocking LtxA-Cholesterol binding would have a similar effect. To accomplish this, we synthesized a peptide based on the cholesterol-binding site of the toxin. We found that this peptide likewise inhibits LtxA from killing host cells. Together, these results demonstrate that receptor-based peptides are an effective strategy to inhibit bacterial toxin activity.
About Shailagne Yutuc
Shailagne Yutuc is currently a junior at Lehigh University, majoring in Chemical Engineering. She has had an interest in finding alternatives to antibiotics, which led her to join the Brown lab as an undergraduate researcher in the summer after her freshman year. She has enjoyed it so much that she has continued the research throughout the academic years. Outside of lab, Shailagne is a Rossin Junior Fellow, the Vice President of Asian Cultural Society, and the Professional Development Chair of AIChE. After graduating, she plans to work in the pharmaceutical industry.
