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Aly Dissertation2.38 MB
Embargoed Access, Embargo ends: 06/26/2027
Dissertation
STAGE-DEPENDENT BACTERIAL EXTRACELLULAR VESICLES COMBAT DRUG-RESISTANCE PATHOGENS
Washington State University
Doctor of Philosophy (PhD), Washington State University
05/2025
DOI:
https://doi.org/10.7273/000007314
Abstract
Drug-resistance pathogens e.g., Pseudomonas aeruginosa are highly resistant to stress conditions, become hospital monsters, and cause severe infections and death. Because known drugs are inherently inactive to treat these infections, solutions are urgently needed. I aimed to investigate the potential applications of applying bacterial extracellular vesicles (EVs) extracted from P. aeruginosa PAO1 to combat drug-resistant pathogens. I hypothesized that bacterial biofilms secrete EVs to connect with other cells in their biofilm community, these EVs carry dependent-growth signals that control biofilm behavior, and if extracted during the disaggregation/lyses phase (D-EVs), they carry growth inhibitor-signal proteins and regulate programmed cell death (PCD). I implemented two aims to test my hypothesis. First, explore the dual effect of P. aeruginosa PAO1 G-EVs and D-EVs on P. aeruginosa PAO1 biofilms. Second: comprehensive proteomic analysis of Pseudomonas aeruginosa (PAO1) biofilm cells, and their corresponding EVs extracted at different growth phases.
My research results exhibited that PAO1-EVs carry unique proteins that fingerprint their role as messengers to coordinate the cellular activities of neighboring cells and facilitate the establishment of a biofilm community. Growth EVs (G-EVs) and disaggregation/cell lyses EVs (D-EVs) display opposite bioactivity results on mature P. aeruginosa PAO1 biofilms (24-h biofilms). G-EVs accelerated the growth of PAO1 biofilms whereas D-EVs inhibited the growth of biofilms. Moreover, D-EVs can effectively prevent the formation of fresh P. aeruginosa PAO1 biofilms. D-EVs can effectively inhibit 96h P. aeruginosa PAO1 biofilms under depleted nutrition conditions when 50μM of Fe3+ ions were supplemented.
I was one of the first to report on the functional role of bacterial EVs in managing cultural growth, and their proteomics differences based on the growth phase of their parental biofilm cells. Altogether, my results examine the burgeoning field of bacterial EV research and focus on drug-resistance pathogens.
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Details
- Title
- STAGE-DEPENDENT BACTERIAL EXTRACELLULAR VESICLES COMBAT DRUG-RESISTANCE PATHOGENS
- Creators
- Marwa Gamal Saad Zaghloul Mohamed Aly
- Contributors
- WEN-JI DONG (Chair)HALUK BEYENAL (Committee Member)ANITA VASAVADA (Committee Member)STEVEN R. SAUNDERS (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Voiland College of Engineering and Architecture
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 115
- Identifiers
- 99901220449001842
- Language
- English
- Resource Type
- Dissertation