Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37644
Title: EXPLORING THE MOLECULAR BASIS OF DRUG RESISTANCE TO PA-824 AND TMC207
Authors: HANA LEI HAVER
Keywords: TMC207, PA-824, spontaneous mutant, Mycobacterium tuberculosis, fitness, resistance
Issue Date: 29-Nov-2012
Source: HANA LEI HAVER (2012-11-29). EXPLORING THE MOLECULAR BASIS OF DRUG RESISTANCE TO PA-824 AND TMC207. ScholarBank@NUS Repository.
Abstract: The threat of drug resistant Mycobacterium tuberculosis (Mtb) hinders global efforts to halt the progression of this epidemiological challenge and there is a great demand for novel anti-tubercular medicines to add to the current standard treatment regimen. Addressing this need, we evaluated the frequency and genetic basis of mycobacterial resistance to PA-824 and TMC207. Combining a forward genetics and a population genetics approach, spontaneous resistant mutants in H37Rv Mtb and Mycobacterium bovis Bacille Calmette-Guerin (BCG) were selected against PA-824 and TMC207. Using polymerase chain reaction (PCR) and Sanger sequencing, resistant strains were characterized mutation type and tested for fitness. Among PA-824-resistant strains, we characterized 8 novel SNPs on ddn, 2 novel mutations on fgd1 and among TMC207-resistant strains, we confirmed 4 previously identified SNPs on atpE. Identifying the types of mutations associated with drug resistance to PA-824 and TMC207 may ultimately serve useful in the development of mutation-specific diagnostic tools.
URI: http://scholarbank.nus.edu.sg/handle/10635/37644
Appears in Collections:Master's Theses (Open)

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