Advisor(s)
Susan Birket
Committee Member(s)
Megan Kiedrowski
Stefanie Krick
Terje Dokland
W Edward Swords
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Joint Health Sciences
Date of Award
9-9-2024
Abstract
Cystic fibrosis (CF) is an autosomal-recessive genetic disease characterized by recurrent and chronic airway infections. Staphylococcus aureus is currently the most common organism isolated from the CF lung, but its role as a pathogen has been historically difficult to characterize due to a broad range of genetic diversity and subtypes seen across infectious strains. Small colony variants (SCVs) are a subpopulation of S. aureus marked by slow growth rate and impaired metabolism that have been associated with worse respiratory outcomes in people with CF (pwCF). SCVs also exhibit altered colony morphology and can confound the results of traditional diagnostic assays, making them difficult to identify in a clinical setting. For these reasons, little is known regarding the direct impact of SCV infection on patient health or how they are acquired in pwCF. In this work, we evaluated whether exposure to factors of the CF airway environment can promote S. aureus SCV formation and investigated the role of SCVs in the progression of CF lung disease both alone and in conjunction with Pseudomonas aeruginosa, a common co-colonizer of the CF lung. We found that exposure to the anti-pseudomonal antibiotic tobramycin and the CFTR potentiator ivacaftor led to the formation of S. aureus SCVs which displayed increased antibiotic tolerance in vitro, suggesting that similar exposures may drive SCV formation and contribute to S. aureus persistence in pwCF. Using the CF rat as a model of airway disease, we found that acute infection with S. aureus SCVs caused more severe disease compared to infection with normal colony variants (NCVs), indicated by increased neutrophilic inflammation in the lung. However, we also found that infection with SCVs may protect the CF lung from developing structural damage and functional decline during chronic co-infection with P. aeruginosa, indicating that the pathogenic role of SCVs may differ depending on external factors such as co-infection. Collectively, this work suggests that infection with S. aureus SCVs may impact the overall progression of CF lung disease and highlights the importance of identifying and characterizing SCVs to inform future treatment approaches for pwCF suffering from respiratory infections.
ProQuest ID
Recommended Citation
Bollar, Gretchen E., "Investigating the Impacts of Staphylococcus aureus Small Colony Variant Infection in the Cystic Fibrosis Rat Lung" (2024). All ETDs from UAB. 7624.
https://digitalcommons.library.uab.edu/etd-collection/7624
