Dual-mechanism adjuvant catharanthine restores β-lactam efficacy against Staphylococcus aureus infections

Dual-mechanism adjuvant catharanthine restores β-lactam efficacy against Staphylococcus aureus infections | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 12 May 2026 V1 Latest version Share on Dual-mechanism adjuvant catharanthine restores β-lactam efficacy against Staphylococcus aureus infections Authors : Jian Zhang [email protected] , Heng Wang [email protected] , Xinyue He [email protected] , Xin Wen [email protected] , Qi Wang [email protected] , Lei Xu [email protected] , yanhong deng [email protected] , and Peng Zhang [email protected] Authors Info & Affiliations https://doi.org/10.22541/authorea.15003039/v1 Under Review British Journal of Pharmacology Peer review timeline 42 views 14 downloads Contents Abstract Graphical Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose： Staphylococcus aureus ( S. aureus) remains a major global health threat with high mortality, causing both community-associated and hospital-acquired infections. Consequently, resistance mechanisms, notably β-lactamase production and biofilm formation, are considered promising therapeutic targets. In this study, catharanthine is an alkaloid compound extracted from the Madagascar periwinkle plant, was a potent adjuvant for β-lactam antibiotics against S. aureus. Experimental Approach: Molecular docking was performed to evaluate the binding interaction between catharanthine and β-lactamase. Metabolomic analysis was used to investigate the effect of catharanthine on bacterial metabolic pathways, particularly those associated with biofilm formation. In addition, murine models of S. aureus pneumonia and skin infection were established to assess the therapeutic efficacy of combination treatment with catharanthine and cefixime in vivo. Results: Catharanthine showed high-affinity binding to β-lactamase in molecular docking analysis, supporting its potential role as a β-lactam antibiotic adjuvant. Metabolomic profiling revealed that catharanthine perturbed the arginine biosynthesis pathway, which is closely associated with biofilm formation, thereby inhibiting biofilm development. In vivo, combination therapy with catharanthine and cefixime effectively alleviated infection in murine models of S. aureus pneumonia and skin infection. Conclusion and Implications: This study demonstrates that catharanthine enhances the therapeutic efficacy of β-lactam antibiotics through dual targeting of β-lactamase-associated resistance and biofilm formation. These findings suggest that catharanthine-based combination therapy may reduce the antibiotic dosage required for treatment and provide a clinically feasible strategy for combating MRSA infections. Graphical Abstract Supplementary Material File (supporting information.docx) supporting information Download 163.65 KB Information & Authors Information Version history V1 Version 1 12 May 2026 Peer review timeline Under Review British Journal of Pharmacology 16 May 2026 Under Review Collection British Journal of Pharmacology Authors Affiliations Jian Zhang [email protected] View all articles by this author Heng Wang [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Xinyue He [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Xin Wen [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Qi Wang [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Lei Xu [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author yanhong deng [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Peng Zhang [email protected] The First Hospital of Jilin University Department of Thoracic Surgery, Changchun, China, 130021 View all articles by this author Metrics & Citations Metrics Article Usage 42 views 14 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jian Zhang, Heng Wang, Xinyue He, et al. Dual-mechanism adjuvant catharanthine restores β-lactam efficacy against Staphylococcus aureus infections. Authorea . 12 May 2026. DOI: https://doi.org/10.22541/authorea.15003039/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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