Advisor(s)
Megan Kiedrowski
Committee Member(s)
Juan Calix
Stephine Krick
Susan Birket
T Prescott Atkinson
Document Type
Dissertation
Date of Award
6-1-2026
Degree Name
Doctor of Philosophy (PhD)
School
Joint Health Sciences (Interdisciplinary)
Department
Joint Health Sciences
Abstract
Staphylococcus aureus is a Gram-positive pathobiont and is a common cause of lung infections in both diabetes and in people with cystic fibrosis (CF). Both of these diseases cause increased glucose availability in the lungs, and there is a strong correlation between glucose availability and S. aureus lung infections. Despite this, there have been few studies examining how glucose availability in the lungs impacts infection outcomes. In the first part of this work, we use both CF and non-CF bronchial epithelial cells cultured at air-liquid interface to model the airway. We cultured cells in normal or hyperglycemic media to model diabetes and non-diabetic states. Using this model, we found that we could accurately model the glucose availability in the airway, and upon infecting cells with S. aureus, we found hyperglycemia altered bacterial aggregation in CF hyperglycemic infections. Additionally, we found S. aureus had increased antibiotic resistance in hyperglycemic culture conditions. In the second part of this work, we aimed to discover the mechanism driving in-creased antibiotic resistance we observed in hyperglycemia. We found that reactive oxygen species (ROS) are significantly higher in CF cells cultured under hyperglycemic conditions. Additionally, we found that adding antioxidants to co-culture infections restored antibiotic effectiveness. We also found that blocking the polyol metabolic pathway prevented the in-crease in ROS. Taken together, these data suggest the hyperglycemic lung environment is promoting S. aureus infection in a ROS-dependent manner, leading to the development of antibiotic resistance. Diabetic wound studies have seen similar development of resistance but did not define a mechanism. This study is the first to provide a mechanism for the development of S. aureus antibiotic resistance in hyperglycemia in the airways.
Recommended Citation
Hughes, Emily, "Staphylococcus Aureus Antimicrobial Susceptibility In Cystic Fibrosis" (2026). ETDs from 2020-2029. 153.
https://digitalcommons.library.uab.edu/etd-2020s/153
