Date of Thesis

Spring 2024

Description

Antibiotic resistance of bacteria is a growing crisis in medical systems around the world. Antimicrobial peptides (AMPs) are being studied as a new approach to combat antibiotic resistant bacteria. A number of AMPs are currently in clinical trials for a variety of applications, but further research is required to develop AMPs with broad applicability to fight systemic bacterial infections. AMPs are short (20 - 80 amino acids) chains of amino acids that are produced by a wide variety of organisms, including insects, which are divided into a number of families based on their amino acid makeup. Here, I am focusing on the cecropin family of AMPs of Drosophila melanogaster. Three cecropin AMPs are produced by D. melanogaster upon infection (CecA, CecB, and CecC) and I determined whether minimal amino acid changes between the three sequences have any effect on the biophysical properties and/or the antimicrobial behavior of these peptides. I analyzed differences in the amino acid sequences of the three peptides using a number of modeling techniques to hypothesize that mutations in the expected hinge region of the AMPs will affect the structural and antimicrobial properties of the peptides. In addition to the natively expressed D. melanogaster cecropin AMPs, I made several point mutations to better compare locations with divergent amino acids across the sequences. I measured the minimum inhibitory concentration (MIC), or the concentration of peptides at which bacteria can no longer grow, of each peptide against six different bacterial species at two different temperatures (25 °C and 37 °C). There was a significant difference in MIC values for the peptides against P. sneebia, P. burhodogranariea B, and P. burhodogranariea D. I discovered that the residue in position 24 in the hinge region has a significant impact on antimicrobial activity and our mutant peptides behaved as expected to confirm this hypothesis.

Keywords

peptides, antimicrobial, synthesis, bacteria

Access Type

Honors Thesis (Bucknell Access Only)

Degree Type

Bachelor of Science

Major

Chemistry

First Advisor

Sarah Smith

Available for download on Thursday, April 29, 2027

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