Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge, necessitating novel therapeutic strategies. This study demonstrates the synergistic bactericidal activity of citral, a phytochemical, and azithromycin against clinical MRSA isolates. Checkerboard assays confir...

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Main Authors: Hitesh K. Sharma, Ibha Singh, Amarnath Karna, Puneet Gupta, Taru Singh, Anoop Kumar, Deepti Pandita, Monalisa Mukherjee, Virinder S. Parmar, Pallavi Agarwal, Viney Lather
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-11721-4
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Summary:Abstract Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge, necessitating novel therapeutic strategies. This study demonstrates the synergistic bactericidal activity of citral, a phytochemical, and azithromycin against clinical MRSA isolates. Checkerboard assays confirmed synergy with a fractional inhibitory concentration index (FICI) of 0.093, while time-kill kinetics showed a reduction in bacterial viability from 5.39 to 2.94 log10 CFU/ml, outperforming monotherapy. Scanning electron microscopy revealed severe cellular damage, indicative of membrane disruption and protein leakage. Notably, the combination extended post-antibiotic effects (PAE) by 4.26 h at MIC, suggesting prolonged antibacterial action. Cytotoxicity assays on normal human fibroblasts demonstrated 93.7% viability at the combined MIC, underscoring its biocompatibility. These findings highlight citral-azithromycin synergy as a promising strategy to enhance antibiotic efficacy against MRSA while minimizing cytotoxicity, supporting the potential of phytochemical-adjuvant combinations in combating antimicrobial resistance.
ISSN:2045-2322