title: Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin.
abstract: OBJECTIVE
  Increasing antimicrobial resistance has compromised the effectiveness of many antibiotics, including those used to treat staphylococcal infections like methicillin-resistant Staphylococcus aureus. The development of combination therapies, where antimicrobial agents are used with compounds that inhibit resistance pathways is a promising strategy. Results/methodology: The Raf kinase inhibitor GW5074 exhibited selective in vitro activity against Gram-positive bacteria, including clinical isolates of S. aureus with a minimum inhibitory concentration (MIC) of 2-8 µg/ml. GW5074 was effective in vivo in the Galleria mellonella infection model. The compound showed synergy with gentamicin by lowering MIC by fourfold, compared with gentamicin MIC alone.
  
  
  CONCLUSIONS
  This work demonstrates the antimicrobial properties of GW5074 and supports further investigation of the kinase inhibitors as antibiotic adjuvants.
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Johnston
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Gabriel Lambert
authors.initials: GL
authors.lastname: Hendricks
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Roy Fangxing
authors.initials: RF
authors.lastname: Chen
authors.affiliation: Department of Neurology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Bumsup
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Illawarra Health & Medical Research Institute, School of Chemistry, University of Wollongong, NSW, Australia.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Kelso
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Burgwyn Fuchs
authors.affiliation: Department of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
keywords: GW5074; Staphylococcus aureus; gentamicin