AbstractsMedical & Health Science

Includes abstract. Tuberculosis, a common and deadly infectious disease is caused by the pathogen Mycobacterium tuberculosis. The recent emergence of multi-drug and extreme multidrug resistant strains poses an even greater obstacle to controlling the disease, particularly in areas where efficient and effective health systems have not been properly addressed. Current treatments using first line drugs typically require extended use and strict compliance by patients, which is often not adhered to. As a result, there is an urgent need for new and highly effective drugs to combat this disease. Mycobacterium tuberculosis relies on mycothiol, a low molecular mass thiol used to circumvent oxidative stress generated by activated macrophages and to deal with antibiotics such as rifamycin. Enzymes involved in the biosynthesis of mycothiol have been elucidated over the past ten years and some have been designated to be essential in the growth of Mtb, with mycothiol disulfide reductase (Mtr) being one. Mtr is involved in the reduction of oxidized mycothiol (MSSM) to mycothiol (MSH) upon exposure of the microbe to oxidative stress. The rationale behind this study involves the use of naphthoquinones grafted onto the mycothiol template as subversive substrates against Mtr. Initially, we had planned to clone and express Mtr in Corynebacterium glutamicum (C. glutamicum) to try to obtain enhanced expression levels of Mtr, and although the expression of the enzyme was not successful we were able to confirm that C. glutamicum does indeed depend on MSH as has been previously suggested but not actually proven. MSH was isolated from C. glutamicum with the aid of a new derivatising agent 2-bromoacetonaphthone (BAN) and characterized using a combination of NMR and mass spectrometry.