Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2013.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2013
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| Online Access: | http://hdl.handle.net/1721.1/80985 |
| _version_ | 1811095401502081024 |
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| author | Kern, Suzanne E |
| author2 | Dianne K. Newman. |
| author_facet | Dianne K. Newman. Kern, Suzanne E |
| author_sort | Kern, Suzanne E |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2013. |
| first_indexed | 2024-09-23T16:16:10Z |
| format | Thesis |
| id | mit-1721.1/80985 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T16:16:10Z |
| publishDate | 2013 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/809852019-04-10T09:10:33Z Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa Kern, Suzanne E Dianne K. Newman. Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2013. "June 2013." Cataloged from PDF version of thesis. Includes bibliographical references. Phenazines are redox-active small molecules produced by bacteria. Although phenazines have been studied extensively for their roles as toxins, how phenazines benefit producing organisms is still being uncovered. Pseudomonas aeruginosa is a phenazine-producing Gram-negative bacterium that inhabits soil and water, and can establish persistent infections in plants, animals, and humans. P. aeruginosa produces phenazines upon activation of its quorum-sensing system, which is involved in numerous physiological changes, including biofilm development. Phenazines have been proposed to aid catabolism of P. aeruginosa under conditions like those found in biofilms-rich in nutrients but low in suitable respiratory oxidants, e.g., oxygen and nitrate-and phenazines are known to oxidize nicotinamide adenine dinucleotides (NAD(P)H) and thereby affect biofilm structure and development. The work in this thesis demonstrates that P. aeruginosa PA14 can survive under anoxic conditions in the presence of glucose and oxidized endogenous phenazines, including pyocyanin, 1-hydroxyphenazine, and phenazine-1-carboxylic acid. Exogenous oxidants such as methylene blue, paraquat, and 2,6-anthraquinone disulphonate, do not support anaerobic survival, suggesting that phenazine survival is an evolved trait that enhances the fitness of P. aeruginosa. Phenazines enable anaerobic survival with glucose but not succinate, and pyruvate fermentation is important for this process. Phenazine redox cycling yields higher levels of ATP, likely by facilitating the oxidation of glucose to pyruvate and acetate by recycling NAD(P)H to NAD(P)+. ATP hydrolysis through the FoF1 ATPase sustains a membrane potential, which is necessary for survival. Similar results were observed for both pyruvate and arginine fermentation. Common features across these survival conditions included NADH/NAD+ ratios less than 3, a polarized membrane, and higher ATP levels than those measured in conditions that do not sustain viability. To perform this work, robust methods for quantifying NADH/NAD+ and phenazines were developed and are described herein. The findings of this thesis represent an important step forward in our understanding of how phenazines physiologically benefit the organisms that produce them. Furthermore, they point us to a more general model of survival for the opportunistic pathogen P. aeruginosa. by Suzanne E. Kern. Ph.D. 2013-09-24T19:35:06Z 2013-09-24T19:35:06Z 2013 Thesis http://hdl.handle.net/1721.1/80985 857788424 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 184 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Kern, Suzanne E Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title | Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title_full | Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title_fullStr | Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title_full_unstemmed | Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title_short | Consequences of redox-active phenazines on the physiology of the opportunistic pathogen Pseudomonas aeruginosa |
| title_sort | consequences of redox active phenazines on the physiology of the opportunistic pathogen pseudomonas aeruginosa |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/80985 |
| work_keys_str_mv | AT kernsuzannee consequencesofredoxactivephenazinesonthephysiologyoftheopportunisticpathogenpseudomonasaeruginosa |