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

2 thoughts on “Battling increasing cases of multi-drug resistant tuberculosis by modifying current treatments”

  1. I do not have very much knowledge at all about bacterial resistance so I found this summary extremely interesting. It would be intriguing to watch how the drug and bacteria actually interact, both when the bacteria has a resistance and when it does not. I wonder if the resistance is actually related to the location of the action site, or if the entirety of the strain has a resistance against any contact with the drug. If the researchers were able to use the x-ray crystallography to study the interaction, I would be curious what the limitations may be to study the resistant strain and drug interacting. I think watching and studying that interaction may be even more helpful in developing a drug that can overcome the resistance in the strain.

  2. Antibiotic resistance is a growing problem in health care. I think it is important to raise awareness about the causes of resistance such as overuse of antibiotics. I was unaware before reading this that tuberculosis is such a widespread cause of death. This makes it an even more pressing matter to search for solutions to the issue of resistance. I find it interesting how x-ray crystallography was used to evaluate the site of drug interaction. It seems like a great observational tool since it was able to identify a site that was not yet targeted. I expect that this will become a more popular route for identifying drug targets and am interested to see what other drugs have been studied in this way.

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