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Antibacterial and antivirulence activities of auranofin against Clostridium difficile.
Int J Antimicrob Agents. 2019 Jan; 53(1):54-62.IJ

Abstract

Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last two decades, C. difficile infections (CDIs) have become a national concern because of the emergence of hypervirulent mutants with increased capability to produce toxins and spores. This has resulted in an increased number of infections and deaths associated with CDI. The scarcity of anticlostridial drugs has led to unsatisfactory cure rates, elevated recurrence rates and permitted enhanced colonization with other drug-resistant pathogens (such as vancomycin-resistant enterococci) in afflicted patients. Therefore, both patients and physicians are facing an urgent need for more effective therapies to treat CDI. In an effort to find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral antirheumatic drug that has recently been found to possess antibacterial activity. Auranofin exhibited potent activity against C. difficile isolates, inhibiting growth at a concentration of 1 µg/mL against 50% of all tested isolates. Auranofin inhibited both toxin production and spore formation, a property lacking in both vancomycin and metronidazole (the primary agents used to treat CDI). Auranofin had a direct protective activity against C. difficile toxin-mediated inflammation and inhibited the growth of vancomycin-resistant enterococci. Auranofin is a promising candidate that warrants further investigation as a treatment option for C. difficile infections.

Authors+Show Affiliations

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN 47907, USA. Electronic address: mseleem@purdue.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30273668

Citation

AbdelKhalek, Ahmed, et al. "Antibacterial and Antivirulence Activities of Auranofin Against Clostridium Difficile." International Journal of Antimicrobial Agents, vol. 53, no. 1, 2019, pp. 54-62.
AbdelKhalek A, Abutaleb NS, Mohammad H, et al. Antibacterial and antivirulence activities of auranofin against Clostridium difficile. Int J Antimicrob Agents. 2019;53(1):54-62.
AbdelKhalek, A., Abutaleb, N. S., Mohammad, H., & Seleem, M. N. (2019). Antibacterial and antivirulence activities of auranofin against Clostridium difficile. International Journal of Antimicrobial Agents, 53(1), 54-62. https://doi.org/10.1016/j.ijantimicag.2018.09.018
AbdelKhalek A, et al. Antibacterial and Antivirulence Activities of Auranofin Against Clostridium Difficile. Int J Antimicrob Agents. 2019;53(1):54-62. PubMed PMID: 30273668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibacterial and antivirulence activities of auranofin against Clostridium difficile. AU - AbdelKhalek,Ahmed, AU - Abutaleb,Nader S, AU - Mohammad,Haroon, AU - Seleem,Mohamed N, Y1 - 2018/09/28/ PY - 2018/06/19/received PY - 2018/09/14/revised PY - 2018/09/22/accepted PY - 2018/10/3/pubmed PY - 2019/4/23/medline PY - 2018/10/2/entrez KW - Anti-toxin KW - Antibacterial KW - Auranofin KW - C. difficile infection KW - Repurposing KW - Spores formation SP - 54 EP - 62 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 53 IS - 1 N2 - Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last two decades, C. difficile infections (CDIs) have become a national concern because of the emergence of hypervirulent mutants with increased capability to produce toxins and spores. This has resulted in an increased number of infections and deaths associated with CDI. The scarcity of anticlostridial drugs has led to unsatisfactory cure rates, elevated recurrence rates and permitted enhanced colonization with other drug-resistant pathogens (such as vancomycin-resistant enterococci) in afflicted patients. Therefore, both patients and physicians are facing an urgent need for more effective therapies to treat CDI. In an effort to find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral antirheumatic drug that has recently been found to possess antibacterial activity. Auranofin exhibited potent activity against C. difficile isolates, inhibiting growth at a concentration of 1 µg/mL against 50% of all tested isolates. Auranofin inhibited both toxin production and spore formation, a property lacking in both vancomycin and metronidazole (the primary agents used to treat CDI). Auranofin had a direct protective activity against C. difficile toxin-mediated inflammation and inhibited the growth of vancomycin-resistant enterococci. Auranofin is a promising candidate that warrants further investigation as a treatment option for C. difficile infections. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/30273668/Antibacterial_and_antivirulence_activities_of_auranofin_against_Clostridium_difficile_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(18)30277-2 DB - PRIME DP - Unbound Medicine ER -