1. Epidemiology of Mycobacterium tuberculosis
Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis is one of the toughest pathogens encountered by mankind. The first remnants of this bacterium were found in the mummies of the pyramids and even till today, 1/3rd of theworld`s population still harbors the bacteria in latent or dormant form although around 90% of them never show any symptoms of disease during their lifetime. According to the WHO report of the year 2016, there were 10.4 million new TB cases worldwide in the year 2015 out of which there were 480 000 new cases of MDR TB.Besides, there were an estimated 1.4 million TB deaths in 2015 with an additional 0.4 million deaths resulting from TB disease among people suffering from HIV.
2. Current Chemotherapy and its pitfalls
The current drug regimen comprises of four frontline drugs namely isoniazid, rifampicin, ethambutol and pyrazinamide, which to date, has provided great armor against Mycobacterium tuberculosis. The duration of the treatment of drug susceptible M. tb generally varies from 6 to 9 months with the administration of four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) for two months and isoniazid and rifampicin for the remaining period. Apart from these frontline drugs, there is a number of second line and third line drugs as well for the treatment of resistant strains of M. tb. Various drug molecules currenty in the market target various pathways of M. tb. The first line and second line drugs target mycolic acid synthesis (ethambutol, isoniazid and ethionamide), protein synthesis (rifampicin), and nucleic acid synthesis (quinolones targeting the DNA gyrase and paramino salicylic acid and para-aminobenzoic acid targeting the folate pathway) (figure 1). Recently, totally drug resistant strains of this pathogen have also been isolated from various parts of the world that have made the situation even more precarious. The lengthy duration of the current chemotherapy leads to non-compliance by a number of patients, which ultimately leads to the emergence of drug resistant strains further complicating the treatment of a patient (1-4). Thus, there is a dire need to devise new effective intervention strategies for combating the susceptible as well as the resistant strains of M. tb.