PMID- 26895605
OWN - NLM
STAT- MEDLINE
DCOM- 20170106
LR  - 20181113
IS  - 1872-7913 (Electronic)
IS  - 0924-8579 (Print)
IS  - 0924-8579 (Linking)
VI  - 47
IP  - 3
DP  - 2016 Mar
TI  - Repurposing auranofin for the treatment of cutaneous staphylococcal infections.
PG  - 195-201
LID - S0924-8579(16)00012-1 [pii]
LID - 10.1016/j.ijantimicag.2015.12.016 [doi]
AB  - The scourge of multidrug-resistant bacterial infections necessitates the urgent 
      development of novel antimicrobials to address this public health challenge. Drug 
      repurposing is a proven strategy to discover new antimicrobial agents; given that 
      these agents have undergone extensive toxicological and pharmacological analysis, 
      repurposing is an effective method to reduce the time, cost and risk associated 
      with traditional antibiotic innovation. In this study, the in vitro and in vivo 
      antibacterial activities of an antirheumatic drug, auranofin, was investigated 
      against multidrug-resistant Staphylococcus aureus. The results indicated that 
      auranofin possesses potent antibacterial activity against all tested strains of 
      S. aureus, including meticillin-resistant S. aureus (MRSA), 
      vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus 
      (VRSA), with minimum inhibitory concentrations (MICs) ranging from 0.0625mug/mL to 
      0.125mug/mL. In vivo, topical auranofin proved superior to conventional 
      antimicrobials, including fusidic acid and mupirocin, in reducing the mean 
      bacterial load in infected wounds in a murine model of MRSA skin infection. In 
      addition to reducing the bacterial load, topical treatment of auranofin greatly 
      reduced the production of inflammatory cytokines, including tumour necrosis 
      factor-alpha (TNFalpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta) and monocyte 
      chemoattractant protein-1 (MCP-1), in infected skin lesions. Moreover, auranofin 
      significantly disrupted established in vitro biofilms of S. aureus and 
      Staphylococcus epidermidis, more so than the traditional antimicrobials linezolid 
      and vancomycin. Taken together, these results support that auranofin has 
      potential to be repurposed as a topical antimicrobial agent for the treatment of 
      staphylococcal skin and wound infections.
CI  - Copyright (c) 2016 Elsevier B.V. and the International Society of Chemotherapy. All 
      rights reserved.
FAU - Thangamani, Shankar
AU  - Thangamani S
AD  - Department of Comparative Pathobiology, Purdue University College of Veterinary 
      Medicine, West Lafayette, IN, USA.
FAU - Mohammad, Haroon
AU  - Mohammad H
AD  - Department of Comparative Pathobiology, Purdue University College of Veterinary 
      Medicine, West Lafayette, IN, USA.
FAU - Abushahba, Mostafa F N
AU  - Abushahba MF
AD  - Department of Comparative Pathobiology, Purdue University College of Veterinary 
      Medicine, West Lafayette, IN, USA; Department of Animal Hygiene and Zoonoses, 
      Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt.
FAU - Sobreira, Tiago J P
AU  - Sobreira TJ
AD  - Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
FAU - Seleem, Mohamed N
AU  - Seleem MN
AD  - Department of Comparative Pathobiology, Purdue University College of Veterinary 
      Medicine, West Lafayette, IN, USA. Electronic address: mseleem@purdue.edu.
LA  - eng
GR  - HHSN272200700055C/AI/NIAID NIH HHS/United States
GR  - R56 AI114861/AI/NIAID NIH HHS/United States
GR  - R56AI114861/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160123
PL  - Netherlands
TA  - Int J Antimicrob Agents
JT  - International journal of antimicrobial agents
JID - 9111860
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3H04W2810V (Auranofin)
RN  - 59XE10C19C (Fusidic Acid)
RN  - D0GX863OA5 (Mupirocin)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - Auranofin/*therapeutic use
MH  - Biofilms/drug effects
MH  - Cell Line
MH  - Chemokine CCL2/biosynthesis
MH  - *Drug Repositioning
MH  - Drug Resistance, Multiple, Bacterial
MH  - Drug Therapy, Combination
MH  - Female
MH  - Fusidic Acid/therapeutic use
MH  - Humans
MH  - Interleukin-1beta/biosynthesis
MH  - Interleukin-6/biosynthesis
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microbial Sensitivity Tests
MH  - Mupirocin/therapeutic use
MH  - Staphylococcal Skin Infections/*drug therapy/microbiology
MH  - Staphylococcus epidermidis/*drug effects
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC4792765
MID - NIHMS754415
OTO - NOTNLM
OT  - Auranofin
OT  - Inflammatory cytokines
OT  - Multidrug resistance
OT  - Repurposing
OT  - Topical antimicrobials
EDAT- 2016/02/21 06:00
MHDA- 2017/01/07 06:00
PMCR- 2017/03/01
CRDT- 2016/02/21 06:00
PHST- 2015/08/21 00:00 [received]
PHST- 2015/12/18 00:00 [revised]
PHST- 2015/12/27 00:00 [accepted]
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2016/02/21 06:00 [entrez]
PHST- 2016/02/21 06:00 [pubmed]
PHST- 2017/01/07 06:00 [medline]
AID - S0924-8579(16)00012-1 [pii]
AID - 10.1016/j.ijantimicag.2015.12.016 [doi]
PST - ppublish
SO  - Int J Antimicrob Agents. 2016 Mar;47(3):195-201. doi: 
      10.1016/j.ijantimicag.2015.12.016. Epub 2016 Jan 23.