Fowler, Erin
(2023)
Bacteriophages against Colistin-resistant Klebsiella pneumoniae.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Klebsiella pneumoniae is one of the most common causes of hospital-acquired infections, and is becoming increasingly resistant to various agents including colistin, a last resort antibiotic. As there are limited treatment options for these types of infections, bacteriophages active against them are drawing attention as a potential treatment option. To identify such bacteriophages, environmental water samples were screened against five different colistin-resistant clinical strains. As a result, two individual bacteriophages, MC8 and MC9, with activity against a colistin-resistant Klebsiella pneumoniae strain were isolated. Both bacteriophages were exclusively active against K. pneumoniae Sequence Type (ST) 258 clade I strains, except for MC9, which was also active against an additional K. pneumoniae ST433 strain. Sequence analysis of the two bacteriophages showed identical sequences except for a 52 base pair nucleotide deletion in the tail spike gene in MC9. Generation of phage-resistant mutants to each bacteriophage was performed to identify their targets. Upon analysis of the phage-resistant mutant sequences, an insertion sequence was found in the wcaJ gene encoding undecaprenyl-phosphate glucose-1-phosphage transferase. This gene helps catalyze the synthesis of colanic acid, a polysaccharide in the extracellular membrane, and a known attachment point used for phage entry.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
17 May 2023 |
| Date Type: |
Publication |
| Defense Date: |
26 April 2023 |
| Approval Date: |
17 May 2023 |
| Submission Date: |
2 May 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
33 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Infectious Diseases and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
bacteriophages |
| Date Deposited: |
17 May 2023 14:17 |
| Last Modified: |
17 May 2023 14:17 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44835 |
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