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Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model.
Sci Rep. 2020 Apr 29; 10(1):7251.SR

Abstract

Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin's in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (107 CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log10 reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log10 reduction) and oral clindamycin (1.24-log10 reduction), which are used to treat infected PUs clinically. The present study highlights auranofin's potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus.

Authors+Show Affiliations

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN, 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN, 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN, 47907, USA. mseleem@purdue.edu. Purdue Institute for Inflammation, Immunology, and Infectious Disease, 610 Purdue Mall, West Lafayette, IN, 47907, USA. mseleem@purdue.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32350417

Citation

Mohammad, Haroon, et al. "Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus Aureus (MRSA) in an Infected Pressure Ulcer Mouse Model." Scientific Reports, vol. 10, no. 1, 2020, p. 7251.
Mohammad H, Abutaleb NS, Seleem MN. Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model. Sci Rep. 2020;10(1):7251.
Mohammad, H., Abutaleb, N. S., & Seleem, M. N. (2020). Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model. Scientific Reports, 10(1), 7251. https://doi.org/10.1038/s41598-020-64352-2
Mohammad H, Abutaleb NS, Seleem MN. Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus Aureus (MRSA) in an Infected Pressure Ulcer Mouse Model. Sci Rep. 2020 Apr 29;10(1):7251. PubMed PMID: 32350417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Auranofin Rapidly Eradicates Methicillin-resistant Staphylococcus aureus (MRSA) in an Infected Pressure Ulcer Mouse Model. AU - Mohammad,Haroon, AU - Abutaleb,Nader S, AU - Seleem,Mohamed N, Y1 - 2020/04/29/ PY - 2020/02/10/received PY - 2020/04/14/accepted PY - 2020/5/1/entrez PY - 2020/5/1/pubmed PY - 2020/5/1/medline SP - 7251 EP - 7251 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Pressure ulcers (PUs) frequently occur in individuals with limited mobility including patients that are hospitalized or obese. PUs are challenging to resolve when infected by antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA). In this study, we investigated the potential of repurposing auranofin to treat pressure ulcers infected with MRSA. Auranofin's in vitro activity against strains of S. aureus (including MRSA) was not affected in the presence of higher bacterial inoculum (107 CFU/mL) or by lowering the pH in standard media to simulate the environment present on the surface of the skin. Additionally, S. aureus did not develop resistance to auranofin after repeated exposure for two weeks via a multi-step resistance selection experiment. In contrast, S. aureus resistance to mupirocin emerged rapidly. Moreover, auranofin exhibited a long postantibiotic effect (PAE) in vitro against three strains of S. aureus tested. Remarkably, topical auranofin completely eradicated MRSA (8-log10 reduction) in infected PUs of obese mice after just four days of treatment. This was superior to both topical mupirocin (1.96-log10 reduction) and oral clindamycin (1.24-log10 reduction), which are used to treat infected PUs clinically. The present study highlights auranofin's potential to be investigated further as a treatment for mild-to-moderate PUs infected with S. aureus. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32350417/Auranofin_Rapidly_Eradicates_Methicillin-resistant_Staphylococcus_aureus_(MRSA)_in_an_Infected_Pressure_Ulcer_Mouse_Model L2 - http://dx.doi.org/10.1038/s41598-020-64352-2 DB - PRIME DP - Unbound Medicine ER -
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