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Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.

Thangamani S, Younis W, Seleem MN - Sci Rep (2015)

Bottom Line: Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms.Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions.This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.

ABSTRACT
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.

No MeSH data available.


Related in: MedlinePlus

Synergistic activity of ebselen with topical antimicrobials.The Bliss Model for Synergy confirms a synergistic effect, between ebselen and topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) against various resistant strains of S. aureus. Degree of synergy was quantified after 12 h of treatment with ebselen (0.0312 μg/ml) in combination with sub-inhibitory concentrations of topical antimicrobials. (Circle) daptomycin + ebselen, (Square) retapamulin + ebselen, (Triangle) fusidic acid + ebselen and (Inverted triangle) mupirocin + ebselen.
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f7: Synergistic activity of ebselen with topical antimicrobials.The Bliss Model for Synergy confirms a synergistic effect, between ebselen and topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) against various resistant strains of S. aureus. Degree of synergy was quantified after 12 h of treatment with ebselen (0.0312 μg/ml) in combination with sub-inhibitory concentrations of topical antimicrobials. (Circle) daptomycin + ebselen, (Square) retapamulin + ebselen, (Triangle) fusidic acid + ebselen and (Inverted triangle) mupirocin + ebselen.

Mentions: The antimicrobial activity of ebselen in combination with topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) was investigated in vitro by the Bliss model of synergism against four clinical isolates. With the exception of the VRSA5 strain and the antibiotic daptomycin, ebselen acted synergistically with all tested antibiotics against S. aureus clinical isolates (Fig. 7).


Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.

Thangamani S, Younis W, Seleem MN - Sci Rep (2015)

Synergistic activity of ebselen with topical antimicrobials.The Bliss Model for Synergy confirms a synergistic effect, between ebselen and topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) against various resistant strains of S. aureus. Degree of synergy was quantified after 12 h of treatment with ebselen (0.0312 μg/ml) in combination with sub-inhibitory concentrations of topical antimicrobials. (Circle) daptomycin + ebselen, (Square) retapamulin + ebselen, (Triangle) fusidic acid + ebselen and (Inverted triangle) mupirocin + ebselen.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4481386&req=5

f7: Synergistic activity of ebselen with topical antimicrobials.The Bliss Model for Synergy confirms a synergistic effect, between ebselen and topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) against various resistant strains of S. aureus. Degree of synergy was quantified after 12 h of treatment with ebselen (0.0312 μg/ml) in combination with sub-inhibitory concentrations of topical antimicrobials. (Circle) daptomycin + ebselen, (Square) retapamulin + ebselen, (Triangle) fusidic acid + ebselen and (Inverted triangle) mupirocin + ebselen.
Mentions: The antimicrobial activity of ebselen in combination with topical antimicrobials (mupirocin, fusidic acid, retapamulin and daptomycin) was investigated in vitro by the Bliss model of synergism against four clinical isolates. With the exception of the VRSA5 strain and the antibiotic daptomycin, ebselen acted synergistically with all tested antibiotics against S. aureus clinical isolates (Fig. 7).

Bottom Line: Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms.Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions.This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.

ABSTRACT
Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.

No MeSH data available.


Related in: MedlinePlus