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Identification of broad host range phage that antagonize multidrug resistant Pseudomonas aeruginosa and their therapeutic potential to restore antibiotic susceptibility among these pathogens

Lake, Alexandra E
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1594303799535431

Abstract Details

2020, Master of Science (MS), Bowling Green State University, Biological Sciences.
Multidrug resistant (MDR) pathogens are predicted to cause more than ten million annual deaths worldwide by 2050, making bacterial infections the leading cause of death. Although bacteria are evolving resistance to all known antibiotics, no large pharmaceutical companies are involved in drug discovery due to high cost and low profitability; thus, no new antibiotics are available, and the current ones are increasingly becoming ineffective at treating MDR infections. Moreover, recent studies suggest that there are few remaining new antibiotics in the environment left for discovery. Since MDR bacterial infections are predicted to be a major crisis, a new or augmented therapy to treat infections is imperative. Bacteriophage therapy is an alternative solution and has been internationally used for over 100 years. In bacteriophage therapy, phage bind to bacteria through specific protein-protein interactions that result in narrow host range infectivity. Although this specificity is beneficial because the interaction precisely targets a single pathogen, it is also problematic because a single phage usually cannot infect multiple strains of the same bacterial species. The phage discovery process to treat a specific pathogen is both time consuming and phage can fall short of the ability to antagonize multiple infections. Thus, phage with broad host range killing phenotypes are more beneficial when using phage therapy to treat infections caused by a particular pathogen. Therefore, this study set out to isolate phage with broad host range killing phenotypes such that phage that could inhibit more than one MDR pathogen could be found. In this study, 29 phage that antagonize cystic fibrosis (CF) derived MDR Pseudomonas aeruginosa were isolated from equine fecal water, purified, characterized through host range assays, and shown to kill two to eight CF derived MDR P. aeruginosa strains. Since phage have been shown to drive bacterial evolution toward increased antibiotic susceptibility, the analysis of this synergistic relationship among broad host range phage and MDR pathogens is further qualified in this study yielding nine potential mutants whose MICs indicate increased antibiotic susceptibility. Due to the rapidly increasing need for a therapy that resolves infections from a variety of pathogens in the face of global antibiotic resistance, this study is vital, not only for the CF community, but also to the health and survival of humanity.
Hans Wildschutte (Advisor)
George Bullerjahn (Committee Member)
Raymond Larsen (Committee Member)
147 p.
Biology; Biomedical Research; Health; Microbiology; Therapy
phage; phage therapy; bacteriophage; bacteriophage therapy; Pseudomonas aeruginosa; multidrug resistance; antimicrobial resistance; synergy between antibiotics and phage; synergy between phage and antibiotics; antibiotic re-susceptibility; drug resistance

Recommended Citations

Citations

  • Lake, A. E. (2020). Identification of broad host range phage that antagonize multidrug resistant Pseudomonas aeruginosa and their therapeutic potential to restore antibiotic susceptibility among these pathogens [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1594303799535431

    APA Style (7th edition)

  • Lake, Alexandra. Identification of broad host range phage that antagonize multidrug resistant Pseudomonas aeruginosa and their therapeutic potential to restore antibiotic susceptibility among these pathogens. 2020. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1594303799535431.

    MLA Style (8th edition)

  • Lake, Alexandra. "Identification of broad host range phage that antagonize multidrug resistant Pseudomonas aeruginosa and their therapeutic potential to restore antibiotic susceptibility among these pathogens." Master's thesis, Bowling Green State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1594303799535431

    Chicago Manual of Style (17th edition)

bgsu1594303799535431
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This open access ETD is published by Bowling Green State University and OhioLINK.