Publication Date

Spring 2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Advisor

Laura C. Miller Conrad

Keywords

C. elegans, LasI, Pseudomonas aeruginosa, quorum sensing, Streptomyces, volatile fatty acids

Subject Areas

Chemistry

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium capable of causing severe infectious disease. Due to its rugged defenses and ability to acquire antibiotic resistance, a new strategy of fighting P. aeruginosa infection is necessary. Unlike antibiotics, antivirulence therapeutics disarm bacteria and make them less virulent instead of affecting their growth. One antivirulence strategy is to target quorum sensing, a signaling pathway that controls virulence genes in P. aeruginosa. Quorum sensing is triggered by a signal molecule produced by the synthase enzyme LasI. We synthesized a small collection of inhibitors designed to competitively inhibit LasI thereby disrupting quorum sensing and virulence. Caenorhabditis elegans is a soil dwelling nematode and a model organism for understanding metazoan nervous systems. C. elegans can be observed exhibiting a strong avoidance response to certain bacterial supernatants. We hypothesized this response is the result of an evolutionarily developed avoidance to fatty acids secreted by Streptomyces spp. We identified the presence of decanoic and dodecanoic acid in cell-free supernatant of multiple Streptomycetes and confirmed C. elegans avoidance response is triggered by these compounds.

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