Date of Award

Spring 1-1-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Ryan T. Gill

Second Advisor

Kenneth Krauter

Third Advisor

Corrie Detweiler

Abstract

Antimicrobial peptides (AMPs) produced from naturally occurring peptides have recently become a focus for drug design. These synthetic derivatives are relatively small (6-12 amino acids), potent, not easily resisted, and active against a broad-range of pathogens; making such compounds particularly attractive as platforms for the development of novel antimicrobials. However, the mode of action of these synthetic peptides, as well as many naturally occurring peptides, remains largely uncharacterized. This lack of understanding, and more specifically the absence of detailed knowledge of the complexity of AMP mode(s) of action, continues to limit our capabilities for taking full advantage of these compounds (Mangoni, Papo et al. 2004). This work was designed to understand the mode(s) of action of the AMPs Bac8c (a synthetic AMP) and histone (naturally occurring AMP), and mode(s) of resistance to these compounds using high-throughput genomic tools and classic genetic approaches. I found that both peptides have different mechanism of action against Bacteria. Bac8 is more complex and a specific target may not be found. It is possible that Bac8c is a “dirty drug” and target multiple complexes within the cell. Histones however, we found were mainly pore formers, and the main mode of resistance against them is through colanic acid biosynthesis.

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