Scribner, Michelle Rachel
(2022)
Parallel genetic adaptations to antibiotics, nutrients, and lifestyle by Pseudomonas aeruginosa.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Microbial evolution has critical implications for human health, from the increasing prevalence of antimicrobial resistance to the pathoadaptation of microbial populations during infection. The evolution of opportunistic pathogen Pseudomonas aeruginosa within the respiratory tract of people with cystic fibrosis is a prime example. Though ubiquitous within the environment, P. aeruginosa evolves new traits in vivo which contribute to reduced clearance of infection and consequent morbidity and mortality. Elucidating the mechanisms and dynamics by which pathogens, including P. aeruginosa, evolve is central to the efficacy of attempts to predict and control pathogen evolution.
In this work, we used evolution experiments to examine the influence of genetic background and environmental factors on adaptation of P. aeruginosa. We investigated the impact of three factors at play within the host environment: antibiotic pressure, nutrient availability, and biofilm lifestyle on selected genes and their evolutionary dynamics. P. aeruginosa populations were propagated in media mimicking the nutrient environment of the cystic fibrosis airways and analyzed using longitudinal whole genome sequencing of evolved populations. First, we determined the evolutionary pathways through which P. aeruginosa evolves resistance to the aminoglycoside antibiotic tobramycin and examined how genetic background affects evolution of drug resistance by comparing with results from identical experiments with Acinetobacter baumannii. In both species, we studied the impact of lifestyle on evolutionary dynamics by propagating populations in both planktonic (well-mixed) and biofilm environments. Populations evolved through strikingly parallel adaptations across lineages, lifestyles, and even species with subtle, but notable, distinctions associated with biofilm lifestyle. In addition, parallel adaptations arose in replicate P. aeruginosa lineages propagated in the absence of drug that changed social interactions in several ways, including altered biofilm formation, quorum sensing, and prophage induction. Remarkably, every environment we examined selected for mutations in pathways commonly mutated during chronic human infection. These findings reveal that the evolution of persistence to stressors, including antibiotics, and rapid genetic and phenotypic diversification are not specific to host conditions. Ultimately, we have learned that P. aeruginosa adaptations to specific host conditions are rapid, somewhat predictable, and generate complex ecological interactions through mutations to regulators of biofilm, quorum sensing, and prophage.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
3 January 2022 |
| Date Type: |
Publication |
| Defense Date: |
9 November 2021 |
| Approval Date: |
3 January 2022 |
| Submission Date: |
16 December 2021 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
200 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Microbiology and Immunology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Pseudomonas aeruginosa, evolution, tobramycin, biofilm, cystic fibrosis, prophage |
| Date Deposited: |
04 Jan 2022 00:50 |
| Last Modified: |
03 Jan 2023 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42120 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}