Advisor(s)
W Edward Swords
Committee Member(s)
Janet Yother
Juan Calix
Megan Kiedrowski
Stefanie Krick
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Microbiology
Date of Award
1-7-2025
Abstract
Achromobacter xylosoxidans is a Gram-negative bacillus that acts as an opportun- istic pathogen in those with cystic fibrosis (CF). Infection with A. xylosoxidans in these populations is associated with decreased lung function. Thus, this raises the question of the role of A. xylosoxidans in CF disease progression. CF is a polymicrobial disease and A. xylosoxidans is oftentimes isolated alongside Pseudomonas aeruginosa, a major CF colonizer. In the context of CF disease, it is important to understand the implications of polymicrobial infection as altered infection dynamics are observed when multiple microbes colonize together. In the first half of this work, we were devoted to understanding A. xylosoxidans colonization, persistence, and virulence. We used respiratory infections in mice with sev- eral closely related strains and saw that strains colonize the lung for up to 72 hours post infection. We saw that strains induced differing levels of inflammation, neutrophilia, and lung damage. We also observed that A. xylosoxidans differentially regulates certain met- abolic and virulence associated genes in a synthetic cystic fibrosis sputum medium (SCFM2) that mimics the chemical composition of the CF lung. In subsequent experiments, we examined concurrent polymicrobial growth and infection with A. xylosoxidans and P. aeruginosa. We utilized in vitro and in vivo models to determine how these two bacteria interact. We observed altered immune responses in polymicrobial infected animals, indicating that responses to infection are attenuated. We also performed RNA-sequencing and observed that in the presence of A. xylosoxidans, P. aeruginosa downregulates phenazine biosynthesis Taken together, these data suggest that A. xylosoxdans is a pathogen of signifi- cance in CF due to its ability to induce lung damage in vivo. Our data show that competition between A. xylosoxidans and P. aeruginosa impacts the immune response to infection and A. xylosoxidans decreases P. aeruginosa tolerance to the major anti- pseudomonal antibiotic, tobramycin. While previous work is mostly epidemiological with regards to these two species, we present an in vivo model showing A. xylosoxidans as a pathogen and demonstrate interactions between this bacterium and P. aeruginosa that indicate antagonism by A. xylosoxidans.
ProQuest ID
Recommended Citation
Billiot, Caitlin E., "Impact Of Achromobacter Xylosoxidans Infection On The Cf Lung In Single-Species And Polymicrobial Infection With Pseudomonas Aeruginosa" (2025). All ETDs from UAB. 7243.
https://digitalcommons.library.uab.edu/etd-collection/7243
