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

Journal Article


Abstract


  • 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


  •   Johnston, Tatiana (external author)
  •   Hendricks, Gabriel Lambert (external author)
  •   Shen, Steven (external author)
  •   Chen, Roy Fangxing (external author)
  •   Kwon, Bumsup (external author)
  •   Kelso, Michael J.
  •   Kim, Wooseong (external author)
  •   Fuchs, Beth (external author)
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2016

Citation


  • Johnston, T., Hendricks, G., Shen, S., Chen, R., Kwon, B., Kelso, M. John., Kim, W., Fuchs, B. Burgwyn. & Mylonakis, E. (2016). Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin. Future Medicinal Chemistry, 8 (16), 1941-1952.

Scopus Eid


  • 2-s2.0-84989910128

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1941

End Page


  • 1952

Volume


  • 8

Issue


  • 16

Place Of Publication


  • United Kingdom

Abstract


  • 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


  •   Johnston, Tatiana (external author)
  •   Hendricks, Gabriel Lambert (external author)
  •   Shen, Steven (external author)
  •   Chen, Roy Fangxing (external author)
  •   Kwon, Bumsup (external author)
  •   Kelso, Michael J.
  •   Kim, Wooseong (external author)
  •   Fuchs, Beth (external author)
  •   Mylonakis, Eleftherios (external author)

Publication Date


  • 2016

Citation


  • Johnston, T., Hendricks, G., Shen, S., Chen, R., Kwon, B., Kelso, M. John., Kim, W., Fuchs, B. Burgwyn. & Mylonakis, E. (2016). Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin. Future Medicinal Chemistry, 8 (16), 1941-1952.

Scopus Eid


  • 2-s2.0-84989910128

Has Global Citation Frequency


Number Of Pages


  • 11

Start Page


  • 1941

End Page


  • 1952

Volume


  • 8

Issue


  • 16

Place Of Publication


  • United Kingdom