Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Ryan Blower

Program: PhD in Biosciences

Date:   Friday April 15, 2016

Time:   2:00 PM
Place:  George Mason University
             Science & Tech (Prince William) Campus<>
            Bull Run Hall, Room 247

Title: "Cationic Antimicrobial Peptides Against Burkholderia and Bacillus"
Committee Chair: Dr. Monique van Hoek
Committee Members:  Dr. Kylene Kehn-Hall, Dr. Iosif Vaisman, Dr. Nitin Agrawal
A copy of the dissertation is available in the Gateway Library.  All are invited to attend the defense.
The rise of antibiotic resistance has driven research into novel antimicrobial therapies. Cationic antimicrobial peptides (CAMPs) are a part of the innate immune system of higher order organisms that have evolved over time to exert host defense and antimicrobial activity.  In this work, pathogens Bacillus anthracis and Burkholderia are investigated for the ability of CAMPs to exert antimicrobial and antibiofilm activity.  Specifically, Burkholderia thailandensis, a Gram-negative soil bacterium used as a model organism for B. pseudomallei, which is the causative agent of melioidosis and is classified as a class B priority pathogen for its potential use as a biological weapon.  We investigated for Burkholderia thailandensis what class of CAMP is most effective at exhibiting antimicrobial activity. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptides, due to multiple resistance systems.  In this work, a number of cationic antimicrobial peptides (CAMPs) and synthetic derivatives were tested against B. thailandensis for both antimicrobial activity and inhibition/dispersion of biofilm formation.  Our results demonstrate that although B. thailandensis is highly resistant to many antibiotics and cyclic peptide antibiotics such as polymyxin B, some antimicrobial peptides, specifically cathelicidin peptides exert antimicrobial and antibiofilm activity towards B. thailandensis.
Bacillus anthracis Sterne strain was also used to study the effect of some canonical classes of antimicrobial peptides.  Several promising CAMPs were identified from several sources including saltwater crocodile, American alligator, and komodo dragon.  Additionally, promising CAMPs were synthetically modified by changing the amino acid sequence slightly to improve peptide activity.  Results shown here will be carried forward to BSL-3 pathogens as well as murine models to further validate results.