Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination

Area of Science:

• Microbiology
• Pharmacology
• Natural Products Chemistry

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical global health threat due to widespread antibiotic resistance.
• Novel therapeutic approaches are urgently needed to overcome MRSA infections.
• Phytochemicals offer potential as adjuncts to existing antibiotics.

Purpose of the Study:

• To investigate the synergistic antibacterial activity of citral and azithromycin against clinical MRSA isolates.
• To evaluate the mechanism of action and biocompatibility of the citral-azithromycin combination.

Main Methods:

• Checkerboard assays were employed to determine synergy (Fractional Inhibitory Concentration Index - FICI).
• Time-kill kinetics assessed bacterial viability reduction.
• Scanning electron microscopy (SEM) visualized cellular damage.
• Cytotoxicity assays were performed on human fibroblasts.

Main Results:

• Synergistic activity confirmed with a FICI of 0.093.
• Bacterial viability decreased significantly (5.39 to 2.94 log10 CFU/ml) compared to monotherapy.
• SEM revealed MRSA membrane disruption and protein leakage.
• The combination demonstrated biocompatibility with 93.7% fibroblast viability at the combined MIC.

Conclusions:

• Citral-azithromycin combination exhibits potent synergistic bactericidal effects against MRSA.
• The synergy involves disruption of bacterial cell membranes.
• This combination represents a promising strategy to enhance MRSA treatment efficacy and potentially mitigate resistance development.