Due to the increase in antibiotic resistant bacteria, there has been renewed interest in using bacteriophage to treat bacterial infections (phage therapy). This body of work examined different aspects related to the interaction between bacteria and phage within a host using the system of Drosophila melanogaster infected with Pseudomonas aeruginosa, which is then treated with lytic bacteriophage. Using this system four specific areas were addressed: I) How in vitro phage life history traits may be predictive of in vivo therapeutic efficacy, II) How the in vivo phage/bacteria dynamics differ for two different phages throughout the course of infection, III) How modification of phage life history traits alters phage therapeutic ability and IV) The variable costs of phage resistance within P. aeruginosa .
The results show that not only can phage therapeutic ability be predicted by phage in vitro fitness, but therapeutic ability can be altered and improved using simple in vitro serial transfer methods. Treatment with different phages shows different dynamics within D. melanogaster as well as bacteria having different levels of phage resistance evolving. Despite phage resistance evolving, we found phage resistance does incur a cost to the bacteria, which results in a decrease in within-host virulence.
In conclusion, addressing these questions not only illustrated the use of D. melanogaster as a good model system for phage therapy, but also provided insight into the complexities of the phage/bacteria interaction within a living host. In addition, beginning to understand the variable costs of phage resistance has extended the knowledge of the complexities behind phage therapy.
|Advisor:||Wang, Ing-Nang, McKean, Kurt|
|Commitee:||Bull, Jim, Caraco, Tom, Pager, Cara|
|School:||State University of New York at Albany|
|School Location:||United States -- New York|
|Source:||DAI-B 75/03(E), Dissertation Abstracts International|
|Subjects:||Microbiology, Evolution and Development|
|Keywords:||Bacteriophage therapy, Experimental evolution, Phage resistance, Pseudomonas aeruginosa|
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