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Bacteriophages against Colistin-resistant Klebsiella pneumoniae

Fowler, Erin (2023) Bacteriophages against Colistin-resistant Klebsiella pneumoniae. Master's Thesis, University of Pittsburgh. (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Fowler, Erinelf63@pitt.eduelf63
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorDoi, Yoheiyod4@pitt.eduyod4
Committee MemberMattila, Joshuajmattila@pitt.edujmattila
Committee MemberMailliard, Robbierbm19@pitt.edurbm19
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


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