{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:19:01Z","timestamp":1793380741597,"version":"4.5.0"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31702200"],"award-info":[{"award-number":["31702200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is a significant zoonotic pathogen with escalating antimicrobial resistance, underscoring the urgent need for novel therapeutics. This study aimed to investigate the therapeutic potential and mechanism of action of the antimicrobial peptide Protegrin-1 (PG-1) against a multidrug-resistant porcine ExPEC strain, PCN033. The minimal inhibitory concentration (MIC) was determined, and resistance stability was assessed through serial induction and withdrawal passages. Hemolytic activity was evaluated to gauge selectivity. A murine infection model was utilized to assess in vivo efficacy, bacterial load reduction, cytokine modulation, and histopathology. Comparative spleen transcriptomic analysis was performed to elucidate global host responses. PG-1 exhibited potent bactericidal activity (MIC = 32 \u03bcg\/mL) and maintained its efficacy over multiple passages, demonstrating no induced resistance. It showed acceptable hemolytic activity and significantly improved survival, reduced bacterial loads in multiple organs, and mitigated tissue damage in mice. Transcriptomics revealed PG-1 treatment broadly tempered infection-induced hyperinflammatory responses, including NF-\u03baB, MAPK, and TNF signaling pathways, and counteracted metabolic reprogramming. The findings conclude that PG-1 effectively integrates direct, resistance-resistant bactericidal activity with multimodal immunomodulation, representing a superior therapeutic strategy that simultaneously eliminates pathogens and restores immune homeostasis, offering a promising alternative to conventional antibiotics against MDR ExPEC infections.<\/jats:p>","DOI":"10.3390\/vetsci12111030","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:47:36Z","timestamp":1761266856000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Protegrin-1 Combats Multidrug-Resistant Porcine ExPEC: Potent Bactericidal Activity and Multimodal Immunometabolic Regulation In Vitro and in a Murine Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinlin","family":"He","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3605-4022","authenticated-orcid":false,"given":"Biao","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0328-9930","authenticated-orcid":false,"given":"Canying","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/S0140-6736(24)01885-3","article-title":"Global burden of antimicrobial resistance and forecasts to 2050","volume":"404","author":"Kariuki","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Meena, P.R., Priyanka, P., and Singh, A.P. 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