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Description
Tuberculosis is a remerging and drug resistant infectious disease caused by Mycobacterium tuberculosis (Mtb). While the majority of tuberculosis (TB) incidences are susceptible cases, a growing proportion of cases are drug resistant. Drug resistance is usually stratified into mono resistance, Multi Drug-Resistance (MDR), Extensively Drug- Resistance (XDR) and Total Drug-Resistance (TDR) TB. Mono resistance is when a strain is resistant to only one anti-TB drug. MDR-TB strains are those resistant to the two most potent first line drugs, Isoniazid (INH), and Rifampin (RIF). Additional resistance to fluoroquinolone group of drugs and to at least one injectable aminoglycoside is defined as XDR-TB. TDR-is not as well defined and is usually understood to be the group of isolates that are resistant to most common anti TB drugs. The Global Consortium for Drug-resistant TB Diagnostics (GCDD) was funded by the National Institute of Health (NIH) to develop a rapid molecular test for the diagnosis of resistance to seven popular first and second line drugs namely Isoniazid (INH), Rifampicin (RIF), Ethambutol (ETH), Pyrazinamide (PZA) Amikacin (AMK), Kanamycin (KAN), Capreomycin (CAP), Moxifloxacin (MOX), and Ofloxacin (OFX). This thesis project involved the study of the GCDD genomes for a better understanding of the mechanism of resistance to three aminoglycoside drugs, AMK, KAN, CAP. The project’s primary aim was the identification of potential new mechanisms of resistance for those isolates that lack the expected mutations in the known genes. Through identification of potential new gene markers, we may be able to find a better, more efficient and accurate diagnostic method for TB.
