Inhibitors to Target Isocitrate Lyases of Mycobacterium tuberculosis H37Rv

Tuberculosis, commonly known as TB, is a communicable bacterial disease caused by the members of the Mycobacterium tuberculosis complex (MTBC). MTBC is a group of genetically related Mycobacterial species, including Mycobacterium tuberculosis (Mtb), Mycobacterium africanum, Mycobacterium caprae, Mycobacterium pinnipedii, Mycobacterium microti, Mycobacterium bovis and Mycobacterium canettii. These are slow-growing gram-positive bacteria that can infect humans as well as animals via aerosols transmission [1], [2]. Among all, Mtb is responsible for more than 90% of TB cases in humans, where it mainly infects the lungs but can spread to different body parts, including the nervous system. The other microbial species are rarely known to infect humans and are primarily associated with animals. Depending upon the site of infection, TB can be categorized into Pulmonary, Extrapulmonary, Miliary and Central Nervous System TB. Pulmonary TB is mainly the most common type, where Mtb is colonized in the lungs. The infected patients usually have a cough with mucus resulting in breathing difficulties, fever, weight loss and coughing up blood in severe cases.

TB related to the central nervous system is referred to as tuberculous meningitis, where the Mtb infection reaches surrounding tissues of the brain and spine from other organs. The patients do not show any symptoms in the early stages of tuberculous meningitis but later may develop low fever, headache, tiredness, loss of appetite and stiff neck. Although this disease is rare, as 1-2% of the total TB cases can progress to tuberculous meningitis, the mortality rate is very high, with 15-30% deaths, despite care and treatment.