Tags

Type your tag names separated by a space and hit enter

Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct.
J Biol Inorg Chem. 2009 May; 14(4):507-19.JB

Abstract

Clostridium difficile is a nosocomial pathogen whose incidence and importance are on the rise. Previous work in our laboratory characterized the central role of selenoenzyme-dependent Stickland reactions in C. difficile metabolism. In this work we have identified, using mass spectrometry, a stable complex formed upon reaction of auranofin (a gold-containing drug) with selenide in vitro. X-ray absorption spectroscopy supports the structure that we proposed on the basis of mass-spectrometric data. Auranofin potently inhibits the growth of C. difficile but does not similarly affect other clostridia that do not utilize selenoproteins to obtain energy. Moreover, auranofin inhibits the incorporation of radioisotope selenium ((75)Se) in selenoproteins in both Escherichia coli, the prokaryotic model for selenoprotein synthesis, and C. difficile without impacting total protein synthesis. Auranofin blocks the uptake of selenium and results in the accumulation of the auranofin-selenide adduct in the culture medium. Addition of selenium in the form of selenite or L-selenocysteine to the growth medium significantly reduces the inhibitory action of auranofin on the growth of C. difficile. On the basis of these results, we propose that formation of this complex and the subsequent deficiency in available selenium for selenoprotein synthesis is the mechanism by which auranofin inhibits C. difficile growth. This study demonstrates that targeting selenium metabolism provides a new avenue for antimicrobial development against C. difficile and other selenium-dependent pathogens.

Authors+Show Affiliations

Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, FL 32816-2364, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

19165513

Citation

Jackson-Rosario, Sarah, et al. "Auranofin Disrupts Selenium Metabolism in Clostridium Difficile By Forming a Stable Au-Se Adduct." Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry, vol. 14, no. 4, 2009, pp. 507-19.
Jackson-Rosario S, Cowart D, Myers A, et al. Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct. J Biol Inorg Chem. 2009;14(4):507-19.
Jackson-Rosario, S., Cowart, D., Myers, A., Tarrien, R., Levine, R. L., Scott, R. A., & Self, W. T. (2009). Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct. Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry, 14(4), 507-19. https://doi.org/10.1007/s00775-009-0466-z
Jackson-Rosario S, et al. Auranofin Disrupts Selenium Metabolism in Clostridium Difficile By Forming a Stable Au-Se Adduct. J Biol Inorg Chem. 2009;14(4):507-19. PubMed PMID: 19165513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct. AU - Jackson-Rosario,Sarah, AU - Cowart,Darin, AU - Myers,Andrew, AU - Tarrien,Rebecca, AU - Levine,Rodney L, AU - Scott,Robert A, AU - Self,William Thomas, Y1 - 2009/01/23/ PY - 2008/10/02/received PY - 2009/01/02/accepted PY - 2009/1/24/entrez PY - 2009/1/24/pubmed PY - 2009/6/16/medline SP - 507 EP - 19 JF - Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry JO - J. Biol. Inorg. Chem. VL - 14 IS - 4 N2 - Clostridium difficile is a nosocomial pathogen whose incidence and importance are on the rise. Previous work in our laboratory characterized the central role of selenoenzyme-dependent Stickland reactions in C. difficile metabolism. In this work we have identified, using mass spectrometry, a stable complex formed upon reaction of auranofin (a gold-containing drug) with selenide in vitro. X-ray absorption spectroscopy supports the structure that we proposed on the basis of mass-spectrometric data. Auranofin potently inhibits the growth of C. difficile but does not similarly affect other clostridia that do not utilize selenoproteins to obtain energy. Moreover, auranofin inhibits the incorporation of radioisotope selenium ((75)Se) in selenoproteins in both Escherichia coli, the prokaryotic model for selenoprotein synthesis, and C. difficile without impacting total protein synthesis. Auranofin blocks the uptake of selenium and results in the accumulation of the auranofin-selenide adduct in the culture medium. Addition of selenium in the form of selenite or L-selenocysteine to the growth medium significantly reduces the inhibitory action of auranofin on the growth of C. difficile. On the basis of these results, we propose that formation of this complex and the subsequent deficiency in available selenium for selenoprotein synthesis is the mechanism by which auranofin inhibits C. difficile growth. This study demonstrates that targeting selenium metabolism provides a new avenue for antimicrobial development against C. difficile and other selenium-dependent pathogens. SN - 1432-1327 UR - https://www.unboundmedicine.com/medline/citation/19165513/Auranofin_disrupts_selenium_metabolism_in_Clostridium_difficile_by_forming_a_stable_Au_Se_adduct_ L2 - https://dx.doi.org/10.1007/s00775-009-0466-z DB - PRIME DP - Unbound Medicine ER -