Electronic Theses and Dissertations

Brian Hoffman

Date

2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

Committee Chair

Daniel Baker

Committee Member

Daniel Baker

Committee Member

Abby Parrill-Baker

Committee Member

Jessica A Jennings

Committee Member

Tomoko Fujiwara

Committee Member

Charles Garner

Abstract

Biofilms pose a threat to public health. The National Institutes of Health estimate that biofilms are linked to 65-80% of hospital-related infections. Biofilms are a complex network of bacterial cells contained within an extracellular matrix and are 10-1000 times more resistant to common antibiotic treatments. Bacteria within a biofilm utilize a form of intercellular communication known as quorum sensing to regulate many cellular functions including the secretion of the extracellular matrix and dispersal of planktonic cells. Compounds known as diffusible signaling factors (DSF) regulate the formation/degradation of the extracellular matrix. One family of DSF consist of medium chain fatty acid analogs comprised of a carboxylic acid headgroup, a C2-C3 cis alkene, and an alkyl tail. Cis-2-decenoic acid (C2DA) disperses Gram (+) and Gram (-) bacteria derived biofilm. The work presented here expands our analysis of DSF analogs and their application in the medical field. To analyze the structural stability of C2DA and 2-heptylcylcopropyl-1-carboxylic acid (2CP), HPLC-QQQ-MS was utilized to develop a sensitive quantitative method for the quantitative analysis of DSF analogs. This quantitative method was used to determine DSF sensitivity to both thermal and oxidative degradation. Furthermore, this method was applied in collaboration to determine the elution rates of 2CP from potential biomaterial applications including chitosan, modified metal surfaces, and hydroxy apatite. This work also expands known DSF analogs by using alkoxy substituted benzoic acids as mimics of the cis unsaturation in C2DA. These analogs differ in headgroup (ester or acid) overall chain length (C4-C8) and aliphatic chain position (ortho, meta, para). Findings show that alkoxy benzoic acids function as antibiofilm agents that prevent and disperse bacterial biofilms. In addition, alkoxy benzoic acids are shown to increase the susceptibility of biofilms to antibiotics.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Embargoed until 5/1/2025

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Available for download on Thursday, May 01, 2025

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