Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin

Journal Article

Aim: 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. Conclusion: This work demonstrates the antimicrobial properties of GW5074 and supports further investigation of the kinase inhibitors as antibiotic adjuvants.

Full Text

Duke Authors

Cited Authors

  • Johnston, T; Hendricks, GL; Shen, S; Chen, RF; Kwon, B; Kelso, MJ; Kim, W; Burgwyn Fuchs, B; Mylonakis, E

Published Date

  • October 2016

Published In

Volume / Issue

  • 8 / 16

Start / End Page

  • 1941 - 1952

Published By

Electronic International Standard Serial Number (EISSN)

  • 1756-8927

International Standard Serial Number (ISSN)

  • 1756-8919

Digital Object Identifier (DOI)

  • 10.4155/fmc-2016-0104

Language

  • en