Battling increasing cases of multi-drug resistant tuberculosis by modifying current treatments

With the upcoming renewal of our TB tests, I thought this article was appropriate. Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and accounted for 1.5 million deaths in 2013. Recently, first line treatments of TB are decreasing as multidrug-resistant strains are increasing worldwide. Therefore it is imperative to begin researching how to alter and modify our current treatments to combat drug-resistant strains. Fluoroquinolone antibacterials, such as our top drug ciprofloxacin, target DNA gyrase and are used to treat tuberculosis. DNA gyrase alters the coiling of DNA by breaking its strands and then resealing them. Quinolones work by targeting tuberculosis gyrase and preventing the resealing of the DNA, therefore causing the bacteria to die.

In this study, researchers used x-ray crystallography to generate 3-D models of how TB’s gyrase interacts with various drugs. Through this modeling, researchers have discovered two different sites where drugs could potentially interact. However, they found that current drugs only interact with one of the sites, revealing the untapped potential of the other site, or even the possibility of altering current drugs to interact with both sites at once, therefore decreasing the risk of the bacteria developing resistance. Because of this study, researchers have more information on how quinolones work and have a direction to focus their attention on in an attempt to fight tuberculosis antibiotic resistance.

Blower TR, Williamson BH, Kerns RJ et al. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from mycobacterium tuberculosis. PNAS. 2016; published ahead of print January 20, 2016.

Link to article