{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:04:09Z","timestamp":1753891449679,"version":"3.41.2"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Pseudomonas aeruginosa<\/jats:italic> is an important opportunistic and foodborne disease-related bacterium, and the increasing antibiotic resistance of the pathogen leads to the urgent exploration of new and effective antibacterial agents. In this study, a scorpion peptide derivative HTP2 was designed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>in vitro<\/jats:italic> anti-<jats:italic>P. aeruginosa<\/jats:italic> activity was evaluated using a broth microdilution assay. A mouse model of <jats:italic>P. aeruginosa<\/jats:italic> skin subcutaneous infection was used to evaluate the <jats:italic>in vivo<\/jats:italic> anti-<jats:italic>P. aeruginosa<\/jats:italic> activity of HTP2. The antibacterial mechanism and influence on pathogenic factors of <jats:italic>P. aeruginosa<\/jats:italic> of HTP2 were also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HTP2 could effectively inhibit the growth of <jats:italic>P. aeruginosa<\/jats:italic> cells with low hemolytic activity. HTP2 killed <jats:italic>P. aeruginosa<\/jats:italic> in a concentration-dependent manner, and could damage the membrane, induce ROS accumulation, and interact with nucleic acids. HTP2 could also inhibit biofilm formation, motility, pyocyanin production, and elastase activity of <jats:italic>P. aeruginosa<\/jats:italic>. In the mouse subcutaneous infection model, HTP2 significantly reduced the bacterial load of <jats:italic>P. aeruginosa<\/jats:italic> cells and inhibited inflammatory infiltration in the infection area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HTP2 could effectively kill <jats:italic>P. aeruginosa in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, and had the potential as an anti-<jats:italic>P. aeruginosa<\/jats:italic> agent.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1622282","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:27Z","timestamp":1751347707000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In vitro and in vivo anti-Pseudomonas aeruginosa activity of a scorpion peptide derivative"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhongjie","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yabo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanwu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfang","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengyang","family":"Xin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","year":"2022","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13494","DOI":"10.3390\/ijms232113494","article-title":"Anti-virulence potential of a Chionodracine-derived peptide against multidrug-resistant Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients","volume":"23","author":"Artini","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"11691","DOI":"10.3390\/ijms222111691","article-title":"Antimicrobial peptides: an update on classifications and databases","volume":"22","author":"Bin Hafeez","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.3390\/antiox10060839","article-title":"ROS defense systems and terminal oxidases in Bacteria","volume":"10","author":"Borisov","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.3390\/antibiotics11081060","article-title":"The structures and binding modes of small-molecule inhibitors of Pseudomonas aeruginosa elastase LasB","volume":"11","author":"Camberlein","year":"2022","journal-title":"Antibiotics (Basel)"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e40135","DOI":"10.1371\/journal.pone.0040135","article-title":"Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo","volume":"7","author":"Cao","year":"2012","journal-title":"PLoS One"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12866-020-01889-2","article-title":"Hypertonic glucose inhibits growth and attenuates virulence factors of multidrug-resistant Pseudomonas aeruginosa","volume":"20","author":"Chen","year":"2020","journal-title":"BMC Microbiol."},{"volume-title":"Performance standards for antimicrobial susceptibility testing","year":"2019","key":"ref9"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/nrd3591","article-title":"Designing antimicrobial peptides: form follows function","volume":"11","author":"Fjell","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"10821","DOI":"10.3390\/ijms251910821","article-title":"Enhancing antimicrobial peptide activity through modifications of charge, hydrophobicity, and structure","volume":"25","author":"Gagat","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1128\/Cmr.00036-10","article-title":"Clinical significance of microbial infection and adaptation in cystic fibrosis","volume":"24","author":"Hauser","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.toxicon.2016.11.261","article-title":"The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus","volume":"125","author":"Kazemi-Lomedasht","year":"2017","journal-title":"Toxicon"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s40121-022-00591-2","article-title":"Therapeutic strategies for emerging multidrug-resistant Pseudomonas aeruginosa","volume":"11","author":"Kunz Coyne","year":"2022","journal-title":"Infect. Dis. Ther."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s12602-019-09623-9","article-title":"Bacteriocin of Pediococcus acidilactici HW01 inhibits biofilm formation and virulence factor production by Pseudomonas aeruginosa","volume":"12","author":"Lee","year":"2020","journal-title":"Probiotics Antimicrob. 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Biotechnol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.toxicon.2022.09.004","article-title":"Antimicrobial activity of CT-K3K7, a modified peptide by lysine substitutions from ctry2459 - a Chaerilus tryznai scorpion venom peptide","volume":"218","author":"Li","year":"2022","journal-title":"Toxicon"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e97539","DOI":"10.1371\/journal.pone.0097539","article-title":"Hp1404, a new antimicrobial peptide from the scorpion Heterometrus petersii","volume":"9","author":"Li","year":"2014","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.toxicon.2020.07.028","article-title":"Antibacterial activity of a scorpion-derived peptide and its derivatives in vitro and in vivo","volume":"186","author":"Li","year":"2020","journal-title":"Toxicon"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"926758","DOI":"10.3389\/fcimb.2022.926758","article-title":"Virulence factors of pseudomonas aeruginosa and Antivirulence strategies to combat its drug resistance","volume":"12","author":"Liao","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"105","DOI":"10.4149\/gpb_2009_02_105","article-title":"New strategies for novel antibiotics: peptides targeting bacterial cell membranes","volume":"28","author":"Lohner","year":"2009","journal-title":"Gen. Physiol. Biophys."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.3390\/antibiotics12091400","article-title":"Peptide stapling applied to antimicrobial peptides","volume":"12","author":"Louren\u00e7o","year":"2023","journal-title":"Antibiotics (Basel)"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e00151-20","DOI":"10.1128\/MMBR.00151-20","article-title":"Pseudomonas aeruginosa as a model to study chemosensory pathway signaling","volume":"85","author":"Matilla","year":"2021","journal-title":"Microbiol. Mol. Biol. 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Microbiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e1011221","DOI":"10.1371\/journal.ppat.1011221","article-title":"Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium","volume":"19","author":"Muggeo","year":"2023","journal-title":"PLoS Pathog."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/jobm.201100292","article-title":"2,5-piperazinedione inhibits quorum sensing-dependent factor production in Pseudomonas aeruginosa PAO1","volume":"52","author":"Musthafa","year":"2012","journal-title":"J. Basic Microbiol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"108897","DOI":"10.1016\/j.ijfoodmicro.2020.108897","article-title":"Efficacy of flavourzyme against Salmonella Typhimurium, Escherichia coli, and Pseudomonas aeruginosa biofilms on food-contact surfaces","volume":"336","author":"Nahar","year":"2021","journal-title":"Int. J. 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J. Nanomedicine"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The epidemiology and pathogenesis and treatment of Pseudomonas aeruginosa infections: an update","volume":"81","author":"Reynolds","year":"2021","journal-title":"Drugs"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e21634","DOI":"10.1016\/j.heliyon.2023.e21634","article-title":"The behaviour of Escherichia coli and Pseudomonas aeruginosa in bottled mineral water","volume":"9","author":"Schalli","year":"2023","journal-title":"Heliyon"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/978-981-13-3588-4_14","article-title":"AMPs as anti-biofilm agents for human therapy and prophylaxis","volume":"1117","author":"Shahrour","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e00545","DOI":"10.1002\/mbo3.545","article-title":"Meloxicam inhibits biofilm formation and enhances antimicrobial agents efficacy by Pseudomonas aeruginosa","volume":"7","author":"She","year":"2018","journal-title":"Microbiology"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3390\/pharmaceutics13040438","article-title":"Amphipathic peptide antibiotics with potent activity against multidrug-resistant pathogens","volume":"13","author":"Shi","year":"2021","journal-title":"Pharmaceutics"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"320","DOI":"10.3390\/jfb15110320","article-title":"Innovative strategies and methodologies in antimicrobial peptide design","volume":"15","author":"Verma","year":"2024","journal-title":"J Funct Biomater"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fmicb.2016.00102","article-title":"Antibiofilm and anti-infection of a marine bacterial exopolysaccharide against Pseudomonas aeruginosa","volume":"7","author":"Wu","year":"2016","journal-title":"Front. 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