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. 2022 Dec 4;11(12):1752.
doi: 10.3390/antibiotics11121752.

Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections

Maria Lajarin-Reinares  1   2 , Eloy Pena-Rodríguez  1 , Mariona Cañellas-Santos  3 , Elisabet Rosell-Vives  3 , Pilar Cortés  2 , Montserrat Llagostera Casas  2 , Maria Àngels Calvo  4 , Francisco Fernandez-Campos  1
Affiliations

Repurposing Disulfiram as an Antimicrobial Agent in Topical Infections

Maria Lajarin-Reinares et al. Antibiotics (Basel). .

Abstract

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.

Keywords: DNA arrays; Staphylococcus aureus; Streptococcus pyogenes; antibiotics; antimicrobial resistance; disulfiram; repurposing; skin.

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Conflict of interest statement

M.L.-R., E.P.-R., M.C.-S., E.R.-V., and F.F.-C. are employees of Laboratory Reig Jofre. They belong to the R&D department and do not participate in marketing or commercial activities. The data presented were conducted under general good laboratory practices. The other authors do not declare any conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of disulfiram molecule (D).
Figure 2
Figure 2
Amount of D per strip (n = 5). The results show the mean and standard deviation.
Figure 3
Figure 3
In vitro cell culture studies. HEK001 cell viability with luminometric assay after 72 h post treatment with D. Data are represented as the mean (n = 3) of the cell viability percentage, referring to the untreated cell (negative control) and positive control with 1% of sodium dodecyl sulfate (SDS).
Figure 4
Figure 4
Interaction network of the main altered genes (upregulated and downregulated) for their response to disulfiram. Each gene is represented as a node and each line represents the number of interactions between genes. Image was created using the STRING Database.
See this image and copyright information in PMC

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