Dissertation
Development of Potential Host-Directed Therapeutics to Treat F. Tularensis Infection
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000006347
Abstract
Since their introduction in the 1920s, antibiotics have saved millions of lives. However, bacterial infections remain a leading cause of death globally. Some bacterial species, such as F. tularensis, are particularly difficult to treat due to inherent or conferred mechanisms such as an intracellular niche or resistance to antibiotics. F. tularensis is a Gram-negative zoonotic pathogen and the etiologic agent of tularemia. It is considered one of the most virulent known pathogens, with a low infectious dose, high mortality rate, and broad host range. Tularemia is a reemerging disease in much of the world, and its ability to be weaponized is of particular concern. With no available vaccine and resistance to many antibiotics, tularemia treatment relies on a limited number of effective treatment options, which are associated with treatment failures, high relapse rates, toxicity, and the potential emergence of antibiotic resistant strains. Thus, additional therapeutics are needed to control F. tularensis infection. Host-directed therapeutics (HDTs) have recently been recognized as favorable treatment options, as they target host mechanisms to eradicate or inhibit the growth of bacteria rather than targeting the bacteria directly. HDTs offer several advantages over antibiotics, such as reduced probability of conferred antibiotic resistance, increased species specificity, and lack of necessity to access the bacteria directly. Here, we outline the discovery and first stages of pre-clinical development of 13 potential HDTs which control F. tularensis with little to no toxicity at therapeutic doses. These studies begin to address the need for additional F. tularensis treatment options.
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Details
- Title
- Development of Potential Host-Directed Therapeutics to Treat F. Tularensis Infection
- Creators
- Shannon Allen
- Contributors
- Thomas Kawula (Advisor)Jean Celli (Committee Member)Anders Omsland (Committee Member)Dana Shaw (Committee Member)Qisheng Zhang (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 99
- Identifiers
- 99901087337001842
- Language
- English
- Resource Type
- Dissertation