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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

Cytotoxicity assay in human keratinocyte (HaCat) cells.HaCat cells were treated with different concentration of ebselen ranging from 0 to 128 μg/ml. DMSO was used as a negative control. Cell viability was measured by MTS assay and IC50 of ebselen to cause cytotoxicity in HaCat cells was calculated.
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f4: Cytotoxicity assay in human keratinocyte (HaCat) cells.HaCat cells were treated with different concentration of ebselen ranging from 0 to 128 μg/ml. DMSO was used as a negative control. Cell viability was measured by MTS assay and IC50 of ebselen to cause cytotoxicity in HaCat cells was calculated.

Mentions: Safety of ebselen in mammalian cells was evaluated against human keratinocyte cells (HaCat) by MTS assay. Ebselen did not show toxicity up to 32 μg/ml. The results demonstrated that half maximal inhibitory concentration (IC50) required by ebselen to inhibit 50% of HaCat cells was found to be 58.78 + 0.64 μg/ml (Fig. 4).


Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.

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

Cytotoxicity assay in human keratinocyte (HaCat) cells.HaCat cells were treated with different concentration of ebselen ranging from 0 to 128 μg/ml. DMSO was used as a negative control. Cell viability was measured by MTS assay and IC50 of ebselen to cause cytotoxicity in HaCat cells was calculated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Cytotoxicity assay in human keratinocyte (HaCat) cells.HaCat cells were treated with different concentration of ebselen ranging from 0 to 128 μg/ml. DMSO was used as a negative control. Cell viability was measured by MTS assay and IC50 of ebselen to cause cytotoxicity in HaCat cells was calculated.
Mentions: Safety of ebselen in mammalian cells was evaluated against human keratinocyte cells (HaCat) by MTS assay. Ebselen did not show toxicity up to 32 μg/ml. The results demonstrated that half maximal inhibitory concentration (IC50) required by ebselen to inhibit 50% of HaCat cells was found to be 58.78 + 0.64 μg/ml (Fig. 4).

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