Combating Bacterial Infections with In-Situ Detection and Antibiotic Technology

Abstract

Currently, there is a looming crisis in the field of antibacterial drug therapy. The emergence of antibacterial drug resistance because of poor antibacterial stewardship, coupled with booming elderly populations, economic disparity and climate change leading to societal instability is undoing the successes of the 20th century in combating infectious disease. New approaches and methods are needed to reverse these trends. My dissertation focuses on three key areas: (1) develop a better understanding of device-related biofilm infections, (2) the use of a bacterial specific D-glutamine positron emission tomography tracer for the direct visualization of infection, and (3) the development of an acid-activated antimicrobial strategy. Each of these areas represents an opportunity to reverse the negative trends of the past few decades. A greater understanding of device-related biofilm infections can provide insight to new treatment modalities, direct imaging of infection will allow more accurate diagnosis of infection and help drive preclinical drug discovery by being able to non-invasively track therapy efficacy, while low pH-activated antimicrobial peptides serve as an example of emerging technologies to directly combat resistance under specific conditions found in infections. These are examples of next-generation ideas applied to the development of antibacterial agents, enhanced imaging tools for diagnosis and targeted antibacterial therapies.