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Repurposing auranofin for the treatment of cutaneous staphylococcal infections.
Int J Antimicrob Agents. 2016 Mar; 47(3):195-201.IJ

Abstract

The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625μg/mL to 0.125μg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections.

Authors+Show Affiliations

Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA.Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA; Department of Animal Hygiene and Zoonoses, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, West Lafayette, IN, USA. Electronic address: mseleem@purdue.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26895605

Citation

Thangamani, Shankar, et al. "Repurposing Auranofin for the Treatment of Cutaneous Staphylococcal Infections." International Journal of Antimicrobial Agents, vol. 47, no. 3, 2016, pp. 195-201.
Thangamani S, Mohammad H, Abushahba MF, et al. Repurposing auranofin for the treatment of cutaneous staphylococcal infections. Int J Antimicrob Agents. 2016;47(3):195-201.
Thangamani, S., Mohammad, H., Abushahba, M. F., Sobreira, T. J., & Seleem, M. N. (2016). Repurposing auranofin for the treatment of cutaneous staphylococcal infections. International Journal of Antimicrobial Agents, 47(3), 195-201. https://doi.org/10.1016/j.ijantimicag.2015.12.016
Thangamani S, et al. Repurposing Auranofin for the Treatment of Cutaneous Staphylococcal Infections. Int J Antimicrob Agents. 2016;47(3):195-201. PubMed PMID: 26895605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repurposing auranofin for the treatment of cutaneous staphylococcal infections. AU - Thangamani,Shankar, AU - Mohammad,Haroon, AU - Abushahba,Mostafa F N, AU - Sobreira,Tiago J P, AU - Seleem,Mohamed N, Y1 - 2016/01/23/ PY - 2015/08/21/received PY - 2015/12/18/revised PY - 2015/12/27/accepted PY - 2017/03/01/pmc-release PY - 2016/2/21/entrez PY - 2016/2/21/pubmed PY - 2017/1/7/medline KW - Auranofin KW - Inflammatory cytokines KW - Multidrug resistance KW - Repurposing KW - Topical antimicrobials SP - 195 EP - 201 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 47 IS - 3 N2 - The scourge of multidrug-resistant bacterial infections necessitates the urgent development of novel antimicrobials to address this public health challenge. Drug repurposing is a proven strategy to discover new antimicrobial agents; given that these agents have undergone extensive toxicological and pharmacological analysis, repurposing is an effective method to reduce the time, cost and risk associated with traditional antibiotic innovation. In this study, the in vitro and in vivo antibacterial activities of an antirheumatic drug, auranofin, was investigated against multidrug-resistant Staphylococcus aureus. The results indicated that auranofin possesses potent antibacterial activity against all tested strains of S. aureus, including meticillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625μg/mL to 0.125μg/mL. In vivo, topical auranofin proved superior to conventional antimicrobials, including fusidic acid and mupirocin, in reducing the mean bacterial load in infected wounds in a murine model of MRSA skin infection. In addition to reducing the bacterial load, topical treatment of auranofin greatly reduced the production of inflammatory cytokines, including tumour necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin significantly disrupted established in vitro biofilms of S. aureus and Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid and vancomycin. Taken together, these results support that auranofin has potential to be repurposed as a topical antimicrobial agent for the treatment of staphylococcal skin and wound infections. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/26895605/Repurposing_auranofin_for_the_treatment_of_cutaneous_staphylococcal_infections_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(16)00012-1 DB - PRIME DP - Unbound Medicine ER -