The bacillary response to chemotherapy in preclinical animal models used to evaluate TB drugs
Date
2010
Authors
Hoff, Donald R., author
Lenaerts, Anne J., advisor
Basaraba, Randall Joseph, 1958-, advisor
Olea-Popelka, Francisco Javier, 1974-, committee member
Journal Title
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Volume Title
Abstract
Current drug treatment for tuberculosis (TB) consists of 6 to 9 months of daily multidrug therapy. The long duration of chemotherapy contributes to a high rate of treatment failure as patients fail to adhere to the prescribed regimen. The length of treatment is thought to be necessary to eradicate a small proportion of Mycobacterium tuberculosis bacilli that persist despite effective drug treatment. Developing drugs that target tubercle bacilli in this drug-refractory state must be found in order to shorten standard therapy. However, specific details on the nature of M. tuberculosis persistence are still lacking. Further hindering the drug discovery process is our incomplete knowledge of the how M. tuberculosis infects different animal models used to evaluate preclinical drug candidates. Pulmonary TB infection manifests and develops very differently between species routinely used to test these compounds and with respect to human infection. The main goal of this thesis is to facilitate the development of new, highly effective drugs for TB treatment by improving our understanding of M. tuberculosis persistence and of the animal models used to test experimental compounds in preclinical trials.
Description
Department Head: Edward Arthur Hoover.