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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-11721-4 |
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| author | Hitesh K. Sharma Ibha Singh Amarnath Karna Puneet Gupta Taru Singh Anoop Kumar Deepti Pandita Monalisa Mukherjee Virinder S. Parmar Pallavi Agarwal Viney Lather |
| author_facet | Hitesh K. Sharma Ibha Singh Amarnath Karna Puneet Gupta Taru Singh Anoop Kumar Deepti Pandita Monalisa Mukherjee Virinder S. Parmar Pallavi Agarwal Viney Lather |
| author_sort | Hitesh K. Sharma |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d6fab381ecb543aea6d3b9fc1c3d79dc |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d6fab381ecb543aea6d3b9fc1c3d79dc2025-08-20T03:43:26ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-11721-4Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combinationHitesh K. Sharma0Ibha Singh1Amarnath Karna2Puneet Gupta3Taru Singh4Anoop Kumar5Deepti Pandita6Monalisa Mukherjee7Virinder S. Parmar8Pallavi Agarwal9Viney Lather10Amity Institute of Pharmacy, Amity University Uttar PradeshAmity Institute of Molecular Medicine and Stem Cell Research, Amity UniversityAmity Institute of Molecular Medicine and Stem Cell Research, Amity UniversityAmity Institute of Pharmacy, Amity University Uttar PradeshAmity Institute of Biotechnology, Amity UniversityDepartment of Pharmacology, Delhi Pharmacological Sciences and Research University (DPSRU)Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences & Research (DIPSAR) Delhi Pharmaceutical Sciences and Research UniversityAmity Institute of Click Chemistry and Research Studies, Amity University Uttar PradeshAmity Institute of Click Chemistry and Research Studies, Amity University Uttar PradeshAmity Institute of Molecular Medicine and Stem Cell Research, Amity UniversityAmity Institute of Pharmacy, Amity University Uttar PradeshAbstract 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.https://doi.org/10.1038/s41598-025-11721-4 |
| spellingShingle | Hitesh K. Sharma Ibha Singh Amarnath Karna Puneet Gupta Taru Singh Anoop Kumar Deepti Pandita Monalisa Mukherjee Virinder S. Parmar Pallavi Agarwal Viney Lather Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination Scientific Reports |
| title | Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination |
| title_full | Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination |
| title_fullStr | Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination |
| title_full_unstemmed | Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination |
| title_short | Counteracting methicillin resistant Staphylococcus aureus through novel Citral-Azithromycin combination |
| title_sort | counteracting methicillin resistant staphylococcus aureus through novel citral azithromycin combination |
| url | https://doi.org/10.1038/s41598-025-11721-4 |
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