Kill the Bugs, Selectively

“Today, we have tuberculosis drugs you have to take for nine months, why can’t we find one that works in three days” - Bill Gates. 

Tuberculosis (TB) is a chronic contagious disease caused by  Mycobacterium tuberculosis (M.tb), one of the leading causes of death worldwide. The WHO estimates about one-third of the world’s population is infected with M.tb, 10% of those infected will progress to active TB disease during their lifetime. The tuberculosis pandemic has been declared a global health emergency as the growing resistance of M.tb to Antibiotics coincides with the spread of risk factors such as HIV/AIDS and diabetes. TB is a complex disease. The current TB drug regimen, a product of scientific advances of the 1960s, requires six to nine months of treatment for active, drug-susceptible TB. Unfortunately, many patients do not or cannot complete this treatment. Poor adherence and prescribing practices have led to the emergence of multi- and extensively drug-resistant strains of TB (MDR-TB and XDR-TB) that increasingly defy current medicines and spread throughout many regions of the globe. The incidence of MRD- and XRD- TB demands renewed efforts to develop a novel class of fast-acting anti TB chemotherapeutics.

 

Mycobacterium tuberculosis is one of the few bacterial species with a proteasome. A team of scientists led by researchers from Weill Cornell Medical College  has found that some oxathiazolone compounds kill tuberculosis-causing bacteria by selectively inhibiting mycobacterial proteasomes without affecting human proteasomes. These compounds were showing no apparent toxicity to mammalian cells. The oxathiazolone compounds are the first example of an anti-tubercular agent that inhibits protein breakdown. The ability of brief exposure to oxathiazol-2-one compounds to inhibit M.tb proteasomes permanently makes it a potential target for anti-TB therapy. These  findings  may lead to drugs that destroy TB in the dormant stage of the lifecycle.