Pathogen Membrane Interactions

Unlike polyelectrolyte, amplipathic molecules interact with lipid membranes through electrostatic and hydrophobic interactions. Natural antimicrobial peptides and their synthetic derivatives are amphipathic molecules with broad-spectrum antimicrobial activity, but the underlying mechanism needs clarification. We systematically investigated interactions between model bacterial membranes and a prototypical family of phenylene ethynylene-based antimicrobial oligomers (AMO's) with controllable activity and selectivity. Homologues in this family can be inactive, specifically active against bacteria, or non-specifically active against bacteria and eukaryotic cells. Our results show that antibacterial activity correlates with ability to induce small unilamellar vesicles into an inverted hexagonal phase. Moreover, AMO's with different activity profiles require different minimum threshold concentration of PE lipids to reconstruct the membrane. To test the relevance of PE-requirement observed with model membranes to the activity of AMO, we carried out microbicidal assays in vitro against a PE knockout mutant bacteria strain and its wild-type parent strain. The results show that, although the PE deficient mutant is normally more susceptible than its wild-type parent strain, the mutant strain surprisingly out-survives its wild-type parental strain W3899 in the presence of our AMO, which is consistent with our results from model system.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Materials Science and Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Yang, Lihua

Contributors dc:contributor

• Wong, Gerard C.L.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3314945

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82822