Advisory Committee Chair
Eilliam Edward Swords
Advisory Committee Members
T Prescott Atkinson
Amit Gaggar
Janet Yother
S Vamsee Raju
Document Type
Dissertation
Date of Award
2021
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Bacterial biofilms, or surface-adherent bacterial communities surrounded by a self-produced extracellular polymeric matrix, are ubiquitous. They are found throughout Earth’s ecosystems, in the soil and waterways, and more pressingly for the medical community, they are found within humans. Bacterial biofilms are associated with a multitude of diseases and their involvement significantly complicates treatment given that bacteria growing within a biofilm are extremely more resistant to antibiotics and immune effectors. Thus, the need to better understand biofilm biology and find ways to disrupt and/or sensitize biofilms to medical treatment is significant. The goal of the research presented herein was to investigate the role of nontypeable Haemophilus influenzae (NTHi) biofilms in chronic obstructive disease and study the viability of targeting bacterial redox homeostasis as an anti-biofilm strategy in multiple disease contexts. In the first portion of the research presented herein, we established a NTHi infection model utilizing the smoke exposed ferret COPD animal model. We characterized the infection dynamics of NTHi, particularly we were able to establish that NTHi forms biofilms within the smoke exposed ferret airways, and the host responses to NTHi, and the airway functional and structural changes induced by NTHi infection. Establishing this physiologically relevant model of COPD using the most common bacterial pathogen of COPD sets the stage for significant advancements in our understandings of the complex interactions occurring within the smoke exposed airways. iv Building upon this work, we turned our attention to investigating anti-biofilm strategies by targeting bacterial redox homoeostasis pathways. We went on to generate five thiol redox pathway mutants and characterize their ability to respond to oxidative stress using both in vitro techniques and both a smoke exposed murine infection model and a chinchilla otitis media model. We demonstrated disruption of these genes in the thiol redox pathways sensitized NTHi biofilms to oxidative stress and compromised the ability of NTHi to establish a successful infection in both animal models. Together, highlighting the potentiality of thiol redox homeostasis as a druggable anti-biofilm target that has clinical relevance in multiple NTHi disease contexts.
Recommended Citation
Hunt, Benjamin C., "Studies on Nontypeable Haemophilus Influenzae Biofilm Persistence & Redox Homeostasis in Chronic Bacterial Diseases" (2021). All ETDs from UAB. 553.
https://digitalcommons.library.uab.edu/etd-collection/553
