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Anika_C_Thesis_OhioLink_2021.pdf (2.84 MB)

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Utilizing bacteriophage to evolve antibiotic susceptibility in multidrug-resistant Pseudomonas aeruginosa

Choudhury, Anika Nawar
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1626570706534933

Abstract Details

2021, Master of Science (MS), Bowling Green State University, Biological Sciences.
Pharmaceutical companies have slowed the discovery and development of antibiotics due to low-profit margins. Therefore, antibiotic discovery is at an all-time low, and pathogens have evolved resistance to all currently available drugs. As a result, multi-drug resistant (MDR) bacterial infections are becoming more difficult to treat, especially in individuals at a high risk for infection such as cystic fibrosis (CF) patients. CF is a genetically inherited disease that inhibits or decreases chloride ion transport across epithelial cell membranes, resulting increased mucus viscosity, impairing normal clearance in the lungs. This environment is ideal for bacterial colonization and leads to a chronic lung infection. A major pathogen that colonizes the CF lung over time is Pseudomonas aeruginosa. A promising alternative treatment against MDR P. aeruginosa is bacteriophage therapy which has several advantages compared to antibiotics. First, phage therapy exhibits minimal side effects because phage are highly host-specific and do not inhibit other bacteria that are part of the human microbiome. Second, phage replicate itself exponentially when killing its host; and third, phage can be applied directly to the site of infection. However, like antibiotics, bacteria can evolve resistance to phage. To circumvent the problem of phage and drug resistance, trade-off effects may promote opportunities against both entities that may be exploited to treat MDR infections. I hypothesize that the effectiveness of antibiotics can be restored after selective pressure from bacteriophage. To test this hypothesis, MDR P. aeruginosa strains were exposed to phage in trade-off experiments, and results showed that the evolved phage resistant P. aeruginosa strain became antibiotic susceptible. In one trade-off experiment, a temperate phage recombined in the P. aeruginosa pathogen at a location downstream of a multidrug resistance efflux pump that may directly affect antibiotic susceptibility. In another experiment, a lytic phage was used, and the selected P. aeruginosa strain also showed increased antibiotic sensitivity. It is likely this resistance reflects underlying genetic mechanisms distinct to those that occurred with the temperate phage. Thus, selective pressure from phage may be utilized to evolve MDR pathogens towards antibiotic susceptibility.
Hans Wildschutte, Ph.D (Advisor)
George Bullerjahn, Ph.D (Committee Member)
Ray Larsen, Ph.D (Committee Member)
114 p.
Bioinformatics; Biology; Biomedical Research; Microbiology; Molecular Biology
Bacteriophage; Pseudomonas; aeruginosa; Antibiotic Resistance; qPCR; RT-PCR; rpoD; Gene expression; Efflux pump; Housekeeping gene; Microbial evolution; Trade-off; Phage-Antibiotic synergy; Cystic fibrosis; CF; AMR; Evolution; Prophage; Lysogenic phage

Recommended Citations

Citations

  • Choudhury, A. N. (2021). Utilizing bacteriophage to evolve antibiotic susceptibility in multidrug-resistant Pseudomonas aeruginosa [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1626570706534933

    APA Style (7th edition)

  • Choudhury, Anika Nawar. Utilizing bacteriophage to evolve antibiotic susceptibility in multidrug-resistant Pseudomonas aeruginosa. 2021. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1626570706534933.

    MLA Style (8th edition)

  • Choudhury, Anika Nawar. "Utilizing bacteriophage to evolve antibiotic susceptibility in multidrug-resistant Pseudomonas aeruginosa." Master's thesis, Bowling Green State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1626570706534933

    Chicago Manual of Style (17th edition)

bgsu1626570706534933
268
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This open access ETD is published by Bowling Green State University and OhioLINK.