ANTIBACTERIAL PROPERTIES OF NOVEL AMPHIPHILES: EXPLORING STRUCTURE-ACTIVITY RELATIONSHIPS

Healthcare-acquired infections are a continuing problem in the United States. The CDC reports that the overall annual direct medical costs of healthcare-acquired infections to U.S. Hospitals ranges from $28.4 to $33.8 billion dollars. This project focuses on novel cationic amphiphiles, which are molecules with one or more positively charged head group, and one or more lipophilic tail. These molecules have long served as antimicrobials by inserting themselves into bacterial membranes, which can eventually lead to the leakage of ions and cell death. We are particularly interested in focusing on three novel tetracationic amphiphiles mX-(2,12)2, oX-(2,12)2, and pX-(2,12)2, as well as three novel biscationic amphiphiles mX-(2,n)2, oX-(2,n)2, and pX-(2,n)2 (where m, o, and p represent meta, ortho, and para, respectively and n represents the length of the hydrocarbon tail). Minimum inhibitory concentration (MIC) assays against six strains of bacteria were performed in order to determine the minimum concentration that resulted in visible inhibition of bacterial growth. Tail length affects antibacterial activity. The mX-(2,n)2, oX-(2,n)2, and pX-(2,n) amphiphiles with a 12 carbon atom hydrophobic chain exhibited that a low concentration of amphiphile were effective at killing all strains of bacteria (2-8 uM). The mX-(2,12)2 and pX-(2,12)2 exhibit similar trends, with amphiphiles with a 12 carbon atom hydrophobic chain inhibiting bacteria at a low concentration (2-16 uM). However, oX-(2,n)2 shows a completely different trend, with the 12 carbon atom hydrophobic chain exhibiting high MIC values of 63-250 uM. In the future, combination assays will be performed to provide information about synergistic amphiphiles. Additionally, biofilm assays will be performed to reveal information about the possibility of these amphiphiles to destroy biofilms. The ultimate goal is to determine how changing the structure of an amphiphile affects its function, in order to provide alternative antimicrobials that can be used in the healthcare field.

Additional Abstract Information

Student(s): Stephanie M. Masters

Department: Biology

Faculty Advisor: Dr. Kyle Seifert

Type: Poster

Year: 2017