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Stroke drug kills bacteria that cause ulcers and tuberculosis

Date:
December 20, 2012
Source:
Federation of American Societies for Experimental Biology
Summary:
A drug for ischemic strokes may also treat tuberculosis and ulcers. New research shows the compound, ebselen, to inhibit the thioredoxin reductase system in bacteria, including Helicobacter pylori and Mycobacterium tuberculosis.

A drug currently being used to treat ischemic strokes may prove to be a significant advance in the treatment of tuberculosis and ulcers. In a new research report appearing online in The FASEB Journal, a compound called ebselen effectively inhibits the thioredoxin reductase system in a wide variety of bacteria, including Helicobacter pylori which causes gastric ulcers and Mycobacterium tuberculosis which causes tuberculosis. Thioredoxin and thioredoxin reductase proteins are essential for bacteria to make new DNA, and protect them against oxidative stress caused by the immune system. Targeting this system with ebselen, and others compounds like it, represents a new approach toward eradicating these bacteria.

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"This new antibacterial principle provides better chances of surviving an infection," said Arne Holmgren, M.D., Ph.D., a researcher involved in the work from the Division of Biochemistry in the Department of Medical Biochemistry and Biophysics, at Karolinska Institutet in Stockholm, Sweden. "Since ebselen is also an antioxidant, the present mechanism can be described as a 'two for the price of one' antioxidant action in inflammation, and specific targeting of multi-resistant bacterial complications and sepsis."

Building on previous observations where ebselen has shown antibacterial properties against some bacteria, Holmgren and colleagues hypothesized that the bacteria sensitive to ebselen relied solely on thioredoxin and thioredoxin reductase for essential cellular processes. They investigated this by testing it on strains of E. coli with deletions in the genes for thioredoxin, thioredoxin reductase and the glutaredoxin system. They found that strains with deletions in the genes coding for glutaredoxin system were much more sensitive than normal bacteria. Researchers further tested ebselen against Helicobacter pylori and Mycobacterium tuberculosis, which both naturally lack the glutaredoxin system and are frequently resistant to many commonly used antibiotics, and found both to be sensitive to ebselen.

"As rapidly as these organisms evolve, we need new drugs sooner rather than later," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The fact that these scientists have found a new target for killing some of the most resistant bacteria is great news, but the fact that we already have at least one drug which we could possibly use now makes the news even better."


Story Source:

The above story is based on materials provided by Federation of American Societies for Experimental Biology. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Lu, A. Vlamis-Gardikas, K. Kandasamy, R. Zhao, T. N. Gustafsson, L. Engstrand, S. Hoffner, L. Engman, A. Holmgren. Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione. The FASEB Journal, 2012; DOI: 10.1096/fj.12-223305

Cite This Page:

Federation of American Societies for Experimental Biology. "Stroke drug kills bacteria that cause ulcers and tuberculosis." ScienceDaily. ScienceDaily, 20 December 2012. <www.sciencedaily.com/releases/2012/12/121220143709.htm>.
Federation of American Societies for Experimental Biology. (2012, December 20). Stroke drug kills bacteria that cause ulcers and tuberculosis. ScienceDaily. Retrieved November 1, 2014 from www.sciencedaily.com/releases/2012/12/121220143709.htm
Federation of American Societies for Experimental Biology. "Stroke drug kills bacteria that cause ulcers and tuberculosis." ScienceDaily. www.sciencedaily.com/releases/2012/12/121220143709.htm (accessed November 1, 2014).

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