자료유형  

 학위논문

Control Number  

0017163128

International Standard Book Number  

9798384018131

Dewey Decimal Classification Number  

576

Main Entry-Personal Name  

Kennelly, Corey.

Publication, Distribution, etc. (Imprint  

[S.l.] : Northwestern University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

201 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-02, Section: B.

General Note  

Advisor: Prindle, Arthur.

Dissertation Note  

Thesis (Ph.D.)--Northwestern University, 2024.

Summary, Etc.  

요약Pseudomonas aeruginosa is a frequently multidrug-resistant opportunistic pathogen, a common cause of healthcare-acquired infections, and a premier model organism used for the study of biofilms. This dissertation is composed of two distinct yet complementary projects which have improved our understanding of nucleotide metabolism in this clinically relevant organism.In the first project, the relationship between environmental purines, c-di-GMP signaling, and biofilm formation was investigated. I found that environmental purines reduced c-di-GMP and biofilm formation in a salvage-dependent manner. Based on further investigation, this is likely caused by upstream metabolic control of c-di-GMP precursors. This mechanism is unique because previously identified cues alter c-di-GMP levels by modulating activity of enzymes directly involved in c-di-GMP synthesis or degradation. I also demonstrated that (p)ppGpp likely allows P. aeruginosa to maintain stable levels of GTP and c-di-GMP, particularly in the presence of extracellular guanylate compounds. These findings may have broad significance because these responses may also occur in other organisms. Overall, this first project reveals that purines can act as a cue for bacteria to shift their lifestyle away from the recalcitrant biofilm state by upstream metabolic control of c-di-GMP signaling.In the second project, the method by which environmental purines and pyrimidines are transported was investigated. Little was previously known about the substrate specificity of the 13 putative nucleobase transporters in P. aeruginosa. Using a combination of genetic and chemical approaches, I identified substrates for 10 putative nucleobase transporters in P. aeruginosa. Specifically, the sole allantoin transporter as well as transporters for adenine, guanine, xanthine, uric acid, cytosine, thymine, uracil, and dihydrouracil were identified. Furthermore, at least 5 of the 13 transporters transport hypoxanthine, a molecule which was found to affect biofilm formation in the first project. The redundancy in transport of this molecule highlights its apparent importance. Transporters important for uptake of the potential antimicrobial therapeutics 8-azaguanine, 6-thioguanine, 5-fluorocytosine, and 5-fluorouracil were also identified. The strains generated for this project can act as new tools to address previously difficult-to-test hypotheses relating to nucleobase transport. Overall, this second project provides an initial characterization of the putative nucleobase transporters in P. aeruginosa, significantly advancing our understanding of nucleobase transport in this clinically relevant organism.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Biology.

Subject Added Entry-Topical Term  

Molecular biology.

Index Term-Uncontrolled  

Biofilms

Index Term-Uncontrolled  

Nucleotide signaling

Index Term-Uncontrolled  

Pseudomonas aeruginosa

Index Term-Uncontrolled  

Purines

Index Term-Uncontrolled  

Pyrimidines

Added Entry-Corporate Name  

Northwestern University Driskill Graduate Training Program in Life Sciences

Host Item Entry  

Dissertations Abstracts International. 86-02B.

Electronic Location and Access  

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Control Number  

joongbu:657259