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Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents

The tuberculosis (TB) epidemic remains a major threat to public health globally, and is exacerbated by the escalating number of multi-drug resistant cases. These factors have highlighted the urgent need for new effective therapies or different approaches to augment the efficacy of current anti-TB dr...

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Main Author: Omollo, Charles
Other Authors: Chibale, Kelly
Format: Thesis
Language:English
Published: Department of Chemistry 2017
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access_status_str Open Access
author Omollo, Charles
author2 Chibale, Kelly
author_browse Chibale, Kelly
Omollo, Charles
author_facet Chibale, Kelly
Omollo, Charles
author_sort Omollo, Charles
collection Thesis
description The tuberculosis (TB) epidemic remains a major threat to public health globally, and is exacerbated by the escalating number of multi-drug resistant cases. These factors have highlighted the urgent need for new effective therapies or different approaches to augment the efficacy of current anti-TB drugs. Synergistic drug combinations present a feasible strategy towards expanding TB treatment options. Despite reported successes with combination screening, as well as the current reliance on combination therapy for TB, this approach remains largely underexplored. Evidence suggests that utilizing synergistic combinations might enable existing clinically-approved drugs to be readily re-purposed for TB treatment, including against multi-(MDR) and extensively- (XDR) drug resistant strains for current therapies are often ineffective. This thesis focused on the development and application of improved methods to identify and advance novel drug combinations for TB therapy. There were two key aspects to this work: firstly, exploring mechanisms of synergy between fusidic acid (FSA), a natural product antibiotic, and current anti-TB agents and, secondly, characterizing antibiotic action by delineating bacteriostatic and bactericidal compounds.
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provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2017
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spelling oai:open.uct.ac.za:11427/25432 Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents Omollo, Charles Chibale, Kelly Warner, Digby F Chemistry The tuberculosis (TB) epidemic remains a major threat to public health globally, and is exacerbated by the escalating number of multi-drug resistant cases. These factors have highlighted the urgent need for new effective therapies or different approaches to augment the efficacy of current anti-TB drugs. Synergistic drug combinations present a feasible strategy towards expanding TB treatment options. Despite reported successes with combination screening, as well as the current reliance on combination therapy for TB, this approach remains largely underexplored. Evidence suggests that utilizing synergistic combinations might enable existing clinically-approved drugs to be readily re-purposed for TB treatment, including against multi-(MDR) and extensively- (XDR) drug resistant strains for current therapies are often ineffective. This thesis focused on the development and application of improved methods to identify and advance novel drug combinations for TB therapy. There were two key aspects to this work: firstly, exploring mechanisms of synergy between fusidic acid (FSA), a natural product antibiotic, and current anti-TB agents and, secondly, characterizing antibiotic action by delineating bacteriostatic and bactericidal compounds. 2017-09-26T15:07:12Z 2017-09-26T15:07:12Z 2017 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/25432 eng application/pdf application/pdf Department of Chemistry Faculty of Science University of Cape Town
spellingShingle Chemistry
Omollo, Charles
Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
thesis_degree_str Doctoral
title Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
title_full Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
title_fullStr Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
title_full_unstemmed Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
title_short Developing methods to prioritize in vitro drug combinations against Mycobacterium tuberculosis: fusidic acid as potential combination partner with known antitubercular agents
title_sort developing methods to prioritize in vitro drug combinations against mycobacterium tuberculosis fusidic acid as potential combination partner with known antitubercular agents
topic Chemistry
url http://hdl.handle.net/11427/25432
work_keys_str_mv AT omollocharles developingmethodstoprioritizeinvitrodrugcombinationsagainstmycobacteriumtuberculosisfusidicacidaspotentialcombinationpartnerwithknownantitubercularagents