Pseudomonas Aeruginosa And Tobramycin Effects On Aspergillus Fumigatus Infection In Cystic Fibrosis Airway

Authors

• Tuan Anh Nguyen, University of Alabama at Birmingham

Advisor(s)

T Spencer Poore

Committee Member(s)

Carrie Coleman
Megan Kiedrowski
Susan Birket

School

Joint Health Sciences (Interdisciplinary)

Document Type

Thesis

Department (new version)

Joint Health Sciences

Date of Award

9-9-2024

Abstract

Aspergillus fumigatus (Af) is one of the most common molds in the airways of people with Cystic Fibrosis (pwCF). The infection of Af is often preceded by Pseudomonas aeruginosa (PsA) infection and its correlated treatment. PsA is considered a highly prevalent bacteria in the CF lung. PwCF suffers from complex and sophisticated coinfections within the airway that negatively impact the health outcomes of patients. Despite this, why fungal and bacterial coinfection occurs in pwCF is still being determined. However, abnormal mucus production and its characteristics are suspected of creating an environment that promotes Af germination and disease progression. This study uses an air-liquid interface (ALI) cell culture for mucus and cell studies to study the ability of Af germination in CF. Our study aims to determine if CF mucus promotes Af germination and how preceding PsA infection influences Af germination in the CF airway. We also establish an in vitro model for the coinfection between PsA infection and Af germination in ALI cell culture. Images were analyzed and quantified using ImageJ particle tracking. Descriptive statistics were used to interpret the findings. We found that hyper mucus concentration promotes Af germination regarding CF or non-CF status. Pyocyanin (PYO), a virulence factor from PsA, can promote Af germination in both CF and non-CF mucus. Considering the percentile solids of the mucus, the significant change of mucus component after PYO stimulation could explain the development of Af in the mucus study. Moreover, we found that antibiotic treatment can restore the amount of Af in the mucus compared to previous PsA infections inhibiting Af growth. In the in vitro cell study for the coinfection between PsA and Af, previous PsA infection in the cell culture promote Af infection. In conclusion, abnormal CF mucus contributes to the development of Af germination, and pyocyanin stimulation or previous PsA infection enhances the growth of Af. Later, further detailed investigation of the mucus characteristics and Af germination should be considered to evaluate other factors contributing to the infection. Different methods of imaging the cell study should be employed to study the three dimensions of Af formation within the cell and the interaction with PsA.

ProQuest ID

https://proquest.com/docview/3101937391