Preferred Name

Ariana Simeone

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Graduation

5-7-2020

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Advisor(s)

Kyle Seifert

Kevin Caran

James Herrick

Abstract

Hospital acquired infections, particularly antibiotic resistant infections, are a growing concern due to their infection and mortality rate, as well as their growing economic burden, and it has been estimated that by the year 2050 the associated mortality rate will be around 10 million deaths per year. A solution to this is better means of prevention, and amphiphiles, compounds with at least one hydrophilic head group and at least one hydrophobic tail, are promising candidates for stopping the spread of infectious bacteria. Novel amphiphiles with two bipyridinium head groups, separated by a hydrophobic carbon spacer of varying lengths, and each with a hydrophobic carbon tail of varying lengths, were synthesized and tested for their antibacterial properties using minimum inhibitory concentrations, time kill, and biofilm disruption assays. The amphiphiles were tested on select bacterial species known to be associated with hospital acquired infections. The amphiphiles, 10-B-12-B-10, 10-B-14-B-10, and 12-B-14-B-12 were shown to be the most effective when considering all three antibacterial assays. Both 10-B-12-B-10 and 12-B-14-B-12 had over 70% biofilm disruptions at concentrations of 63μM and 125μM, respectively, exceeding the disruption capabilities of tobramycin at its peak concentrations. Both 10-B-12-B-10 and 10-B-14-B-10 were able to kill three out of the four bacteria tested in 5 minutes or less, with S. aureus being killed in 30 minutes, while 8-B-16-B-8 and 10-B-12-B-10 were able to kill two out of the four tested bacteria in less than one minute. In the 10-tailed series at spacer lengths of 12 and 14 carbons, the growth of all tested bacteria was inhibited at concentrations of 2μM to 4μM. Scanning electron microscopy (SEM) of tested strains showed poration and lysis of the cell membranes was likely the mechanism of action of these amphiphiles. These results can be useful for the development of antiseptics and disinfectants that can effectively prevent the spread of antibacterial resistant bacteria.

Available for download on Wednesday, April 13, 2022

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