Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections
Lajarin-Reinares, Maria (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Pena-Rodríguez, Eloy (Topical & Oral Development. Research and Development Reig Jofre Laboratories)
Cañellas-Santos, Mariona (Biotechnology Department. Research and Development Reig Jofre Laboratories)
Rosell-Vives, E. (Biotechnology Department. Research and Development Reig Jofre Laboratories)
Cortés Garmendia, M. Pilar (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Casas, M.L. (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Calvo Torras, Ma. de los Ángeles (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Fernandez-Campos, Francisco (Topical & Oral Development. Research and Development Reig Jofre Laboratories)

Fecha:	2022
Resumen:	Antimicrobial drugs applied topically offer several advantages. However, the widespread use of antibiotics has led to increasing antimicrobial resistance. One interesting approach in the drug discovery process is drug repurposing. Disulfiram, which was originally approved as an anti-alcoholism drug, offers an attractive alternative to treat topical multidrug resistance bacteria in skin human infections. This study aimed to evaluate the biopharmaceutical characteristics of the drug and the effects arising from its topical application in detail. Microdilution susceptibility testing showed antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. Dermal absorption revealed no permeation in pig skin. The quantification of the drug retained in pig skin demonstrated concentrations in the stratum corneum and epidermis, enough to treat skin infections. Moreover, in vitro cytotoxicity and micro-array analyses were performed to better understand the mechanism of action and revealed the importance of the drug as a metal ion chelator. Together, our findings suggest that disulfiram has the potential to be repurposed as an effective antibiotic to treat superficial human skin infections.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Antibiotics, Vol. 11 Núm. 12 (december 2022) , p. 1752, ISSN 2079-6382

DOI: 10.3390/antibiotics11121752
PMID: 36551409

14 p, 982.6 KB

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