ABSTRACT
AIM: l-benzyl-3-cetyl-2-methylimidazolium iodide (NH125) can inhibit Staphylococcus aureus growth. We investigated the effects of sub-MIC concentrations of NH125 on S. aureus biofilm and virulence. Methodology & results: Three strains of S. aureus were tested. Sub-lethal concentrations of NH125 repressed biofilm formation. At partial sub-MICs, NH125 downregulated the expression of most virulence, while strain-dependent effects were found in the production of α-hemolysin, δ-hemolysin, coagulase and nuclease. In Galleria mellonella model, methicillin-resistant S. aureus pre-exposed to NH125 demonstrated significantly lower killing (p = 0.032 for 1/16 and 1/8 MICs; 0.008 for 1/4 MIC; and 0.001 for 1/2 MIC). CONCLUSION: Sub-MIC concentrations of NH125 inhibited biofilm formation and virulence of S. aureus. These findings provide further support for evaluating the clinical efficacy of NH125 in staphylococcal infection.
Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Imidazoles/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Virulence Factors/metabolism , Coagulase/metabolism , Deoxyribonucleases/metabolism , Enzyme Activation , Hemolysin Proteins/metabolism , Humans , Methicillin-Resistant Staphylococcus aureus/metabolism , Microbial Sensitivity Tests , Staphylococcal Infections , VirulenceABSTRACT
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.
