All ETDs from UAB

Advisory Committee Chair

Jessica A Scoffield

Advisory Committee Members

Megan Kiedrowski

Carlos J Orihuela

W Edwards Swords

Amy Weinmann

Document Type

Dissertation

Date of Award

2023

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The cystic fibrosis airway is a polymicrobial environment often dominated by opportunistic pathogens such as Pseudomonas aeruginosa, a leading cause of lung function decline and mortality in persons with CF. Commensal streptococcal colonization has been associated with stable CF lung function in multiple studies. However, few studies have examined interactions between P. aeruginosa and commensals as well as their impact on P. aeruginosa airway infections. In the first half of this work, we studied interactions between P. aeruginosa and the oral commensal Streptococcus salivarius within a biofilm setting. We found that S. salivarius biofilm formation is promoted by the non-mucoid P. aeruginosa exopolysaccharide Psl in both an in vitro biofilm model and a Drosophila colonization model. Additionally, this interspecies interaction may be mediated by the S. salivarius maltose binding protein MalE. In the second half of this work, we examined the impact of S. salivarius on P. aeruginosa airway infection in a rat co-infection model. The presence of S. salivarius during P. aeruginosa infection led to a significant decrease in P. aeruginosa airway colonization, as well as a substantial decrease in pro-inflammatory cytokines and tissue inflammation. Additionally, downregulation of P. aeruginosa glucose metabolism genes and iv intracellular glucose levels was observed in the presence of S. salivarius, suggesting that S. salivarius may alter P. aeruginosa behavior and fitness. Taken together, these findings highlight competitive and cooperative interactions between P. aeruginosa and S. salivarius. S. salivarius utilizes the P. aeruginosa exopolysaccharide Psl as a potential mechanism for sustaining streptococcal colonization in the CF airway. Additionally, in a rat co-infection model, the presence of S. salivarius reduces P. aeruginosa airway colonization and subsequent lung tissue damage. These studies are the first to explore mechanistic interactions between P. aeruginosa and S. salivarius and impacts of S. salivarius on P. aeruginosa airway infection.

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