All ETDs from UAB

Advisor(s)

Jessica Scoffield

Committee Member(s)

Beatriz Leon-Ruiz
Champion Deivanayagam
Megan Kiedrowski
Michael Gray

School

Joint Health Sciences (Interdisciplinary)

Document Type

Dissertation

Department (new version)

Microbiology

Date of Award

9-11-2025

Abstract

Chronic infections with Pseudomonas aeruginosa are a leading cause of morbidity and mortality in people with cystic fibrosis. P. aeruginosa persists in the CF lung through adaptations, including altering the expression of metabolic genes to acquire nutrients that are abundant in the CF airway. Glycerol in the airway is imported and metabolized by proteins encoded in the glp regulon, which is regulated in part by GlpR. The loss of GlpR was previously shown to increase biofilm development in a P. aeruginosa CF isolate compared to a wound isolate. In the first half of this work, we investigated the influence that GlpR has on the sensitivity of P. aeruginosa to tobramycin. We found both PAO1 ΔglpR and FRD1 ΔglpR are less sensitive to tobramycin than PAO1 and FRD1. RNA sequencing from the strains treated with tobramycin gave some insight into genes that may influence the tobramycin sensitivity. We also began studying changes in virulence phenotypes with GlpR knockout, finding difference in the amount of alginate, pyocyanin and pyoverdine produced. In the second half, we further explored both the role of alginate in changing media dynamics and how GlpR influences motility. We found that FRD1 ΔglpR make SCFM2 more viscous and elastic and this may be due to the increased alginate it produces. Also, we found that motility is decreased overall when GlpR is knocked out in PAO1 and FRD1. We also did chromatin immunoprecipitation sequencing to identify additional genes that GlpR regulates. Together, our findings demonstrate that glycerol metabolism and GlpR are able to influence multiple phenotypes in P. aeruginosa that affect its virulence. Further work may reveal further insights into how P. aeruginosa is able to adapt to the host and modulate its pathogenesis in the host.

Included in

Microbiology Commons

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