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Herein, a novel dodecapeptide, denoted as\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    , was designed and synthesized, aiming to combat these notorious pathogens. Experimental results proved that the simple chirality conversion of the parent peptide,\n                    <jats:bold>zp37<\/jats:bold>\n                    , could significantly boost the antibacterial activity and proteolytic stability. To a specific cephalosporin\u2010resistant\n                    <jats:italic>Vibrio alginolyticus<\/jats:italic>\n                    , the minimal inhibitory concentration value of\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    was as low as 0.5\u00a0\u00b5\n                    <jats:sc>m<\/jats:sc>\n                    . Beyond the strong bacteriolytic effect against planktonic\n                    <jats:italic>Vibrio alginolyticus<\/jats:italic>\n                    ,\n                    <jats:italic>Vibrio parahaemolyticus<\/jats:italic>\n                    and\n                    <jats:italic>Vibrio vulnificus<\/jats:italic>\n                    strains,\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    was found to restrain the biofilm establishment of\n                    <jats:italic>Vibrio<\/jats:italic>\n                    mixtures via inhibiting the efflux of intracellular polysaccharides. Mechanistic studies hinted that\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    impeded the electron transport chain, impaired the membrane stress response by downregulating the phage shock protein family, and blocked amino acid biosynthesis in\n                    <jats:italic>Vibrio<\/jats:italic>\n                    cells. Furthermore, three different infection models (shrimp,\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    larvae and immunosuppressed mice) collaboratively confirmed the anti\u2010\n                    <jats:italic>Vibrio<\/jats:italic>\n                    efficacy of\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    in vivo. In addition, the intragastric administration of\n                    <jats:bold>D\u2010zp37<\/jats:bold>\n                    was found to be beneficial in restoring the imbalanced gut microbiota induced by the polymicrobial\n                    <jats:italic>Vibrio<\/jats:italic>\n                    invasion. In summary, this work investigated the antibacterial mechanisms and in vivo efficacy of a novel peptide lead compound, proposing a new therapeutic against\n                    <jats:italic>Vibrio<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522326","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T19:33:14Z","timestamp":1776367994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Chirality\u2010Converted Bacteriolytic Dodecapeptide Regulates\n                    <i>Vibrio<\/i>\n                    \u2010Induced Polymicrobial Infection and Ameliorates Invasion\u2010Associated Gut Microbiota Disequilibrium"],"prefix":"10.1002","volume":"13","author":[{"given":"Ping","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine The Chinese University of Hong Kong  Shatin Hong 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