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A Cyclic antimicrobial peptide as a potential agent for combating multidrug-resistant 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 Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 10 March 2025 V1 Latest version Share on A Cyclic antimicrobial peptide as a potential agent for combating multidrug-resistant Staphylococcus aureus infections Authors : Demeke Yeshanew , James Mwangi , Brenda Michira , Mehwish Khalid , Prateeksha Prateeksha , Min Yang , Lu Qiumin , Wang Yi , Rebecca Thuku , Zilei Duan , and Ren Lai [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174160716.69405754/v1 305 views 180 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose: Developing potent, broad-spectrum antimicrobial peptides with rapid onset of action can mitigate the growing threat of antimicrobial resistance posed by conventional antibiotics. We designed a cyclic antimicrobial peptide named as SAP 2.8 to evaluate the antibacterial activity and mechanism of action against pathogens. Experimental approach: The antimicrobial activity of various antibiotics and antimicrobial peptides against pathogens was assessed by measuring their minimal inhibitory concentration (MIC). Time kills kinetics, scanning electron microscopy, transmission electron microscopy, and membrane integrity studies were conducted to know the mechanism of action of the peptide. Balb/C and C57BL/6 mice were utilized for the wound infection model and peritonitis model to evaluate the therapeutic potential of the SAP 2.8 peptide in in vivo experiments. Key Results: SAP 2.8 antimicrobial peptide was observed more potent against Staphylococcus aureus and Methicillin-resistant staphylococcus aureus clinical isolates (MICs; 1.25-2.5 µg/mL). SAP 2.8 showed advantages of rapid bactericidal properties within 30 min. Additionally, SAP 2.8 inhibited bacteria biofilm formation and disrupted preformed biofilms in vitro. Mechanistic studies indicated that SAP 2.8 disrupts bacterial cell membranes and leads to an increase in intracellular reactive oxygen species, eventually resulting in bacterial death. Notably, SAP 2.8 demonstrated significant in vivo efficacy against S. aureus and MRSA infections. Conclusion and implications: SAP 2.8 peptide is an excellent candidate to combat bacterial infections both in vitro and in vivo. This shows SAP 2.8, might represent a promising candidate for the treatment of S.aureus skin infections. Supplementary Material File (figure 2.tif) Download 4.60 MB File (figure 3.tif) Download 33.88 MB File (figure 4.tif) Download 3.03 MB File (figure 5.tif) Download 69.00 MB File (manuscript.doc) Download 128.16 MB Information & Authors Information Version history V1 Version 1 10 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anti-microbials bacteria clinical pharmacology in vivo pharmacokinetics systems pharmacology Authors Affiliations Demeke Yeshanew Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author James Mwangi Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Brenda Michira Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Mehwish Khalid Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Prateeksha Prateeksha Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Min Yang Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Lu Qiumin Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Wang Yi Southern Marine Science and Engineering Guangdong Laboratory Zhanjiang View all articles by this author Rebecca Thuku Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Zilei Duan Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Ren Lai [email protected] Kunming Institute of Zoology Chinese Academy of Sciences View all articles by this author Metrics & Citations Metrics Article Usage 305 views 180 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Demeke Yeshanew, James Mwangi, Brenda Michira, et al. A Cyclic antimicrobial peptide as a potential agent for combating multidrug-resistant Staphylococcus aureus infections. Authorea . 10 March 2025. DOI: https://doi.org/10.22541/au.174160716.69405754/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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