Creative Commons License

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

Date of Award

Spring 2015

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Advisor(s)

Kyle Seifert

Abstract

Antibiotic resistant bacteria were first reported in the 1940s, several years after the clinical introduction of penicillin. Since then, antibiotic resistance has contributed to increasing bacterial infections, mortality rates, and treatment costs. One promising alternative to traditional antibiotics is the development and use of amphiphiles, compounds with at least one hydrophilic head group and one hydrophobic tail. Three novel series of triple-headed amphiphiles with variations in the third head group composition, tail length and number of tails (one or two) were synthesized. Isothermal titration calorimetry was used to determine the critical micelle concentration – the concentration at which amphiphiles aggregate and form micelles. The antibacterial activity of individual amphiphiles against six bacterial strains and of binary combinations against two representative strains was determined by standard antimicrobial microdilution techniques. The lowest concentration of amphiphile resulting in 50% hemolysis (EC50) was also determined.

For all three amphiphiles series, log of the critical micelle concentration was inversely proportional to tail length. These series also shared a similar biological trend where antibacterial activity increased with tail length until an optimal tail length was reached (n = 12 for double-tailed amphiphiles; n = 18 for single-tailed amphiphiles). Notably, three compounds (M-P,10,10; M-P,12,12; M-1,12,12) killed multiple bacterial strains at concentrations ranging from 1-16 µM and were not cytotoxic to blood cells, with EC50 values that were two- to 65-fold higher than bactericidal concentrations. In addition, several combinations of amphiphiles exhibited synergistic antibacterial activity. These bactericidal, non-hemolytic amphiphiles could be useful in the medical field, especially when treating or preventing infection with antibiotic resistant pathogens.

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