Cationic antimicrobial peptides (CAPs) offer a viable alternative to conventional antibiotics as they physically disrupt the bacterial membranes, leading to cell lysis and death. However, colonized bacteria often form “biofilms” – characterized by the overproduction of exopolysaccharides - that restrict the penetration of antibiotics; successful antimicrobial agents must evade this exopolysaccharide ‘matrix’ to reach the bacterial membrane. Since the Pseudomonas aeruginosa biofilm alginate traps CAPs by forming peptide-alginate complexes, the aim of this thesis is to better understand the mechanisms of interaction of CAPs with bacterial membranes and biofilm alginate. Using a series of CAPs designed in our lab derived from the sequence KKKKKK-AAFAAWAAFAA-NH2, we found that hydrophobicity, charge distribution, and amino acid composition of CAPs play important roles in their membrane disruptive power, bioactivities, alginate-binding and alginate-diffusion abilities. These findings suggest routes to an optimal balance of factors in CAP design to allow both biofilm penetration and bacterial membrane destruction.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33594 |
| Date | 27 November 2012 |
| Creators | Yin, Lois Menglu |
| Contributors | Deber, Charles M. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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