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

Abstract

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.

• Authors: Tatiana Johnston, Gabriel Lambert Hendricks, Steven Shen, Roy Fangxing Chen, Bumsup Kwon, Michael John Kelso, Wooseong Kim, Beth Burgwyn Fuchs, Eleftherios Mylonakis
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 8 Issue 16 Pg. 1941-1952 (Oct 2016) ISSN: 1756-8927 [Electronic] England
• PMID: 27652456 (Publication Type: Journal Article)