{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:50:50Z","timestamp":1775710250461,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T00:00:00Z","timestamp":1775260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing prevalence of multidrug-resistant (MDR) pathogens, particularly avian pathogenic Escherichia coli (APEC) and methicillin-resistant Staphylococcus aureus (MRSA), poses a severe threat to the breeding industry and human health. To develop novel antibiotic alternatives, we adopted a \u201cconverting virulence into therapy\u201d strategy by leveraging the type VI secretion system (T6SS) of the APEC strain ACN17-20. Guided by the structural analysis of T6SS Protein 00145, we rationally designed a series of amphipathic \u03b1-helical polypeptides. Among them, polypeptide A7 emerged as a lead candidate, exhibiting potent broad-spectrum antibacterial activity with negligible cytotoxicity against mammalian cells. Mechanistic studies revealed that A7 exerts a rapid bactericidal effect through a dual mode of action: physical disruption of bacterial membrane integrity leading to cytoplasmic leakage, and induction of lethal oxidative stress via reactive oxygen species (ROS) accumulation. Furthermore, A7 demonstrated excellent efficacy in eradicating pre-formed bacterial biofilms, addressing the challenge of persistent infections in breeding environments. In a mouse sepsis model induced by APEC and MRSA, A7 treatment significantly improved survival rates (60\u201380%), reduced bacterial loads in vital organs, and attenuated the systemic cytokine storm (TNF-\u03b1 and IL-1\u03b2), thereby alleviating immune-mediated tissue damage. In conclusion, this study identifies polypeptide A7 as a safe therapeutic agent with a dual mechanism of action, providing a promising strategy to combat MDR infections and reduce antibiotic dependence.<\/jats:p>","DOI":"10.3390\/ijms27073277","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T02:06:21Z","timestamp":1775441181000},"page":"3277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Virulence to Therapy: T6SS-Derived Antimicrobial Peptides A7 Combats APEC and MRSA Infections"],"prefix":"10.3390","volume":"27","author":[{"given":"Qin","family":"Lu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoran","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingping","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary, Hubei Academy of Agricultural Sciences, Wuhan 430064, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial resistance: A global multifaceted phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. 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