Researcher ORCID Identifier

https://orcid.org/0009-0005-2704-0779

Graduation Year

2024

Date of Submission

4-2024

Document Type

Open Access Senior Thesis

Degree Name

Bachelor of Arts

Department

Biology

Reader 1

Pete Chandrangsu

Reader 2

Shibu Yooseph

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© 2024 Cooper M. McKenna

Abstract

The rise of multidrug-resistant (MDR) bacterial pathogens has been a growing concern in healthcare around the world, and bacteriophage (phage) therapy is a promising method to combat MDR infections. One defense mechanism of E. coli against antibiotics is the TolC-AcrAB efflux pump. At the same time, some phages use TolC as a surface receptor to infect the cell. This puts TolC at a crossroads in which it is beneficial to the bacteria to protect against antibiotics but harmful by allowing phage infection, creating the potential for evolutionary trade-offs. Previous research has identified only three TolC-dependent phages and shown phage-resistant E. coli mutants to have decreased antibiotic resistance (antagonistic pleiotropy) but also some cases of increased antibiotic resistance (synergistic pleiotropy), demonstrating a complex interaction. In order to identify new TolC-dependent phages and investigate their interactions with antibiotic resistance mechanisms, samples were collected and spot tested against WT versus ∆TolC E. coli, yielding three phages. Phage-resistant mutant strains were developed and tested for antibiotic resistance using a Kirby-Bauer assay, and nearly all mutants showed decreased antibiotic resistance to all four antibiotics, but one showed increased resistance to one antibiotic. Finally, a genome size of 23 kbp was determined via gel electrophoresis, suggesting they could be the same phage but that the phage(s) is/are novel. These results point to the continued promise of further research on phage therapy or combination therapy with antibiotics, especially by focusing on phages which target bacterial antibiotic resistance mechanisms.

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