Undergraduate Honors Theses

Thesis Defended

Spring 2015

Document Type

Thesis

Type of Thesis

Departmental Honors

Department

Biochemistry

First Advisor

Dr. Daniel Feldheim

Second Advisor

Dr. Joseph Falke

Third Advisor

Dr. Rolf Norgaard

Fourth Advisor

Dr. Steve Schmidt

Abstract

In 2013, the Centers for Disease Control and Prevention (CDC) declared antibiotic resistance a serious health threat to the global community. Multi-drug resistant (MDR) Gram-negative bacteria have become particularly problematic, as very few new classes of small-molecule antibiotics for Gram-negative bacteria have emerged in recent decades. The Feldheim Lab has developed a combinatorial screening process for identifying mixed-ligand monolayer gold nanoparticle conjugates with antibiotic activity. The gold nanoparticle conjugates have been found to be highly active against E. coli. The bacteria develop resistance to the nanoparticles at a significantly slower rate than commercially available small-molecule drugs.

The Feldheim Research Team has shown that the antimicrobial property of the nanoparticles depends on the identity and ratio of the ligands in the monolayer. Altering the ratio of one of the ligands from a conjugate designed for E. coli produced an altered conjugate with high levels of activity towards K. pneumoniae, and turned a bacteriostatic conjugate into a bactericidal conjugate. The altered conjugate also doubled the time to resistance over the initial nanoparticle formulation.

A differential gene expression experiment performed with K. pneumoniae determined that more active conjugates may alter the expression of many cell division proteins unchanged with exposure to less active nanoparticles. In addition, the altered conjugate induced the expression of many antibiotic resistance genes, yet the bacteria remained susceptible to the conjugate for a number of days. The altered gold-nanoparticle conjugate was found to be an effective inhibitor of K. pneumoniae growth, with the possible ability to avoid resistance mechanisms.