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Parallel genetic adaptations to antibiotics, nutrients, and lifestyle by Pseudomonas aeruginosa

Scribner, Michelle Rachel (2022) Parallel genetic adaptations to antibiotics, nutrients, and lifestyle by Pseudomonas aeruginosa. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Scribner, Michelle Rachelmrs186@pitt.edumrs1860000-0003-4244-4200
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorCooper, Vaughn
Committee ChairBomberger, Jennifer
Committee MemberShanks, Robert
Committee MemberRichardson, Anthony
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


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