PMID- 26111644
OWN - NLM
STAT- MEDLINE
DCOM- 20160621
LR  - 20211203
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Jun 26
TI  - Repurposing ebselen for treatment of multidrug-resistant staphylococcal 
      infections.
PG  - 11596
LID - 10.1038/srep11596 [doi]
LID - 11596
AB  - 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-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta), 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.
FAU - Thangamani, Shankar
AU  - Thangamani S
AD  - Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue 
      University, West Lafayette, Indiana, USA.
FAU - Younis, Waleed
AU  - Younis W
AD  - Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue 
      University, West Lafayette, Indiana, USA.
FAU - Seleem, Mohamed N
AU  - Seleem MN
AD  - Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue 
      University, West Lafayette, Indiana, USA.
LA  - eng
GR  - HHSN272200700055C/AI/NIAID NIH HHS/United States
GR  - HHSN272200700055C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150626
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Azoles)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Isoindoles)
RN  - 0 (Organoselenium Compounds)
RN  - 40X2P7DPGH (ebselen)
RN  - D0GX863OA5 (Mupirocin)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Azoles/*pharmacology
MH  - Bacterial Toxins/metabolism
MH  - Biofilms/drug effects/growth & development
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Daptomycin/pharmacology
MH  - Drug Repositioning
MH  - Drug Synergism
MH  - Female
MH  - Host-Pathogen Interactions/drug effects
MH  - Humans
MH  - Isoindoles
MH  - Keratinocytes/drug effects
MH  - Methicillin Resistance/*drug effects
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects/metabolism/physiology
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Mupirocin/pharmacology
MH  - Organoselenium Compounds/*pharmacology
MH  - Skin/drug effects/metabolism/microbiology
MH  - Staphylococcal Infections/*drug therapy/microbiology
PMC - PMC4481386
EDAT- 2015/06/27 06:00
MHDA- 2016/06/22 06:00
PMCR- 2015/06/26
CRDT- 2015/06/27 06:00
PHST- 2015/04/15 00:00 [received]
PHST- 2015/05/21 00:00 [accepted]
PHST- 2015/06/27 06:00 [entrez]
PHST- 2015/06/27 06:00 [pubmed]
PHST- 2016/06/22 06:00 [medline]
PHST- 2015/06/26 00:00 [pmc-release]
AID - srep11596 [pii]
AID - 10.1038/srep11596 [doi]
PST - epublish
SO  - Sci Rep. 2015 Jun 26;5:11596. doi: 10.1038/srep11596.