Pf bacteriophage as novel pathogenic factors in pseudomonas aeruginosa infections
Abstract/Contents
- Abstract
- Pseudomonas aeruginosa is a Gram-negative pathogen that contributes to the morbidity and mortality of a variety of chronic infections. P. aeruginosa is particularly known for infecting the lungs of cystic fibrosis (CF) patients and colonizing non-healing wounds, where its presence is strongly associated with poor clinical outcomes. With the increasing incidence of antibiotic-resistant strains, it is important to gain a better understanding of the virulence factors that contribute to P. aeruginosa pathogenesis, as such knowledge can lead to new effective treatments. One such proposed virulence factor is Pf phage, a family of filamentous bacteriophages specific to P. aeruginosa, which have been found in high numbers in P. aeruginosa biofilm. For the studies outlined in this dissertation, we investigated the impact of Pf phage on P. aeruginosa pathogenesis, both in mouse models and human clinical infections. We describe how Pf phage organize extracellular polymers in the P. aeruginosa biofilm matrix into a protective liquid crystal. Furthermore, we utilized a newly-developed wound infection model to determine that Pf phage contribute to wound colonization, morbidity and mortality through induction of antiviral immunity, which inhibits protective antibacterial immune responses. In addition, we found that active and passive immunization against Pf phage coat protein protect against P. aeruginosa infection. These findings were translated to the clinic, where we found that presence of Pf phage is correlated with chronic infections and poor health in patients with cystic fibrosis and non-healing wounds with P. aeruginosa infections. Ultimately, our investigation of Pf phage provides new mechanistic insights into the pathology of P. aeruginosa colonization and persistence of infection, toward the development of new treatments for patients infected with antibiotic-resistant bacteria.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Sweere, Johanna Maria |
|---|---|
| Degree supervisor | Bollyky, Paul |
| Thesis advisor | Bollyky, Paul |
| Thesis advisor | Cegelski, Lynette |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Monack, Denise M |
| Degree committee member | Cegelski, Lynette |
| Degree committee member | Engleman, Edgar G |
| Degree committee member | Monack, Denise M |
| Associated with | Stanford University, Department of Immunology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Johanna Maria Sweere. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Johanna Maria Sweere
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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