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Phage therapy for treatment of Klebsiella
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Kelly, Lucy (2023) Phage therapy for treatment of Klebsiella. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3957298
Abstract
The increasing global prevalence of antibiotic-resistant Klebsiella spp. is a major cause for concern, as Klebsiella are a common cause of healthcare-associated infections. The antibiotic resistance crisis, coupled with the dearth of new antibiotic development, led to the increase in Klebsiella pneumoniae and Klebsiella oxytoca infections. Hospital-acquired pneumonia and urinary tract infections are commonly caused by Klebsiella, and can develop into life-threatening bloodstream infections if not treated effectively. Mortality rates of Klebsiella infections can be as high as 80%, thus new treatment options for Klebsiella infections are urgently required. Phage therapy offers an alternative to antibiotic treatment for infections caused by antibiotic-resistant Klebsiella.
This thesis will focus on the development of a safe and effective phage cocktail to target Klebsiella in complex models of infection. Bacteria-phage culture studies were used to select the most effective phage combination against a panel of K. pneumoniae and K. oxytoca strains. Different phage doses and treatment timings were examined to select the most effective regime of phage therapy. Phage cocktail safety and efficacy was demonstrated through mammalian cell culture and invertebrate models of Klebsiella colonisation and infection. Phage cocktail treatment reduced cytotoxic effects of K. pneumoniae infection in cell culture, in addition to increasing survival of infected cells. Furthermore, the phage cocktail was also effective at increasing the survival rate of the Galleria mellonella infection model of K. pneumoniae and K. oxytoca. Preliminary safety data for phage cocktail treatment showed no toxic side effects were observed in the animal or mammalian cell culture models.
The initial design of an effective and safe phage cocktail against Klebsiella was shown to be successful across complex models of infection. This approach can consequently be used to inform effective future phage cocktail design and provide a basis for using phage therapy to treat antibiotic-resistant Klebsiella infections.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology |
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Library of Congress Subject Headings (LCSH): | Klebsiella pneumoniae, Bacteriophages -- Therapeutic use, Drug resistance in microorganisms | ||||
Official Date: | March 2023 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | School of Life Sciences | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Jameson, Eleanor | ||||
Format of File: | |||||
Extent: | xiv, 229 pages : colour illustrations, maps | ||||
Language: | eng |
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