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INTERACTIONS WITHIN PSEUDOMONAS AERUGINOSA AND BURKHOLDERIA CEPACIA MIXED-SPECIES CULTURE INVOLVED IN GROWTH AND MULTIDRUG-TOLERANT PERSISTENCE
|Title:||INTERACTIONS WITHIN PSEUDOMONAS AERUGINOSA AND BURKHOLDERIA CEPACIA MIXED-SPECIES CULTURE INVOLVED IN GROWTH AND MULTIDRUG-TOLERANT PERSISTENCE|
|Contributors:||Seifried, Steven (advisor)|
Molecular Biosciences and Bioengineering (department)
|Publisher:||University of Hawai'i at Manoa|
|Abstract:||The opportunistic human pathogens Pseudomonas aeruginosa (Pa) and Burkholderia cepacia (Bc) constitute a major concern for cystic fibrosis and immunocompromised patients. Infections caused by these bacteria are notoriously difficult to treat and contribute significantly to disease progression. Although co-colonization of the cystic fibrosis lung by Pa and Bc can cause more severe and rapid disease development, little is known on how these bacteria interact within the host. Therefore, the overall goal of this project was to, in part, address this lack of knowledge by advancing the current understanding of interactions that occur within Pa and Bc mixed-species culture. The work provided within this dissertation contains the first detailed description of a complex interconnecting network of interactions within mixed-species Pa and Bc biofilms involved in growth and the formation of multidrug-tolerant persistence. |
The negative transcriptional regulator RsaL and the phenazine-modifying enzyme PhzH of Pa were found to aid in the ability of Bc to co-exist with Pa through their shared involvement in suppressing Pa pyocyanin production. This secondary Pa metabolite was found to inhibit Bc growth through the generation of the reactive oxygen species (ROS) hydrogen peroxide and increase production of multidrug-tolerant Bc persister cells via an unknown, ROS-independent, mechanism. It was further discovered that Bc utilizes the predicted alkyl hydroperoxidase RS01075, and potentially iron availability, as defense mechanisms to counteract pyocyanin. Similarly, in mixed-species biofilm, Pa responds to the presence of Bc by increasing the production of its own multidrug-tolerant persister cells. Results from additional investigations provide the first direct evidence for the involvement of the Fic domain toxin PaFicT of Pa in persister cell formation. This novel determinant of persistence was found to be responsible for the majority of Pa persister cells formed in both single and mixed-species biofilms.
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|Appears in Collections:||
Ph.D. - Molecular Biosciences and Bioengineering|
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