A Novel Drug for Tuberculosis

Once rampant across the globe Tuberculosis has been brought under control, first by improved hygiene standards, and then antibiotic drugs, such as isoniazid and rifampicin, developed in the 1950s and 1960s. However, it remains one of the top 10 causes of death across the world, infecting 10.4 million people and killing 1.8 million in 2015, the vast majority (95%) in low- and middle-income countries.[1] Further, there has been a rise of TB strains that are resistant to antibiotics – around 480,000 people developed multi-drug resistant TB (MDR-TB) in 2015.[1] Of these, only 52% were successfully treated by second-line treatment options, such as extensive chemotherapy. More worryingly, there has been a rise in cases developing extensive drug resistance (XDR-TB), which has very limited treatment options. One of the United Nation’s Sustainable Development Goals is to end the TB epidemic by 2030, but to do this new antibiotics are needed to which no resistance has developed.

University of Warwick researcher Gregory Challis, together with Eshwar Mahenthiralingam and colleagues, recently discovered a promising candidate – gladiolin. [2] Bacteria belonging to the genus Burkholderia are able to thrive in a diverse range of environments thanks to their ability to produce potent antibiotics to remove any competition. Researchers were able to isolate gladiolin by screening one such strain, B. gladioli, that was taken from a child with cystic fibrosis. Gladiolin works by inhibiting RNA polymerase (a validated drug target in TB), has significantly improved chemical stability compared to structurally similar antibiotics, and has low cytotoxicity in mammals. Further research found that while gladiolin was less effective (compared to isoniazid and rifampicin) against strains of TB with no resistance, it had good activity against several strains of TB that were resistant to isoniazid and rifampicin. It is hoped that gladiolin will be the starting point for developing new drugs that can tackle MDR-TB and XDR-TB.

— Peter Chilton, Research Fellow

References:

  1. World Health Organization. Tuberculosis Fact Sheet. 2017.
  2. Song L, Jenner M, Masschelein J, et al. Discovery and Biosynthesis of Gladiolin: A Burkholderia gladioli Antibiotic with Promising Activity against Mycobacterium tuberculosis. J Am Chem Soc. 2017; 139(23): 7974-81.
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