{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:46:22Z","timestamp":1782794782539,"version":"3.54.5"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"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. Immunol."],"abstract":"<jats:p>\n                    Acute hepatopancreatic necrosis disease (AHPND), caused by\n                    <jats:italic>Vibrio parahaemolyticus<\/jats:italic>\n                    , poses a severe threat to global shrimp aquaculture. Reduced susceptibility of aquaculture-associated bacterial pathogens to conventional antibiotics,\u00a0together with concerns regarding antimicrobial input and environmental exposure, highlights the need for dose-sparing therapeutic strategies. This study investigated the antibiotic-potentiating activity of honokiol (HKL), a plant-derived lignan, in combination with sulfamonomethoxine sodium (SMM-Na) against AHPND. Checkerboard and time-kill assays demonstrated that sub-inhibitory HKL concentrations (32\u201364 \u03bcg\/mL) markedly enhanced SMM-Na activity, reducing its minimum inhibitory concentration by 8\u201332-fold and achieving bactericidal effects in combination. The SMM-Na + HKL combination also significantly inhibited biofilm formation and compromised bacterial membrane integrity, as evidenced by enhanced propidium iodide uptake and scanning electron microscopy, while inducing severe ATP depletion. In\n                    <jats:italic>Penaeus vannamei<\/jats:italic>\n                    challenged with\n                    <jats:italic>V. parahaemolyticus<\/jats:italic>\n                    , dietary administration of low-dose SMM-Na (16 mg\/kg) and HKL (32 mg\/kg) yielded the highest survival rate (86.6%), substantially reduced hepatopancreatic bacterial load, attenuated histopathological damage, and restored total hemocyte counts. The treatment also upregulated a broad spectrum of immune-related genes (e.g.,\n                    <jats:italic>Alf<\/jats:italic>\n                    ,\n                    <jats:italic>Tlr<\/jats:italic>\n                    ,\n                    <jats:italic>Lec<\/jats:italic>\n                    ,\n                    <jats:italic>Crustin<\/jats:italic>\n                    ,\n                    <jats:italic>Lzm<\/jats:italic>\n                    ,\n                    <jats:italic>CatB<\/jats:italic>\n                    ) in the hepatopancreas and mucosal barrier genes (e.g.,\n                    <jats:italic>Muc-1<\/jats:italic>\n                    ,\n                    <jats:italic>Muc-4<\/jats:italic>\n                    ,\n                    <jats:italic>Muc-5AC<\/jats:italic>\n                    ,\n                    <jats:italic>Muc-19<\/jats:italic>\n                    ) in the intestine. Furthermore, 16S rRNA sequencing indicated that the combination therapy was associated with treatment-related shifts in the intestine microbiota, including increased alpha diversity indices, reduced\n                    <jats:italic>Vibrio<\/jats:italic>\n                    abundance, and altered predicted KEGG functional profiles. Collectively, our results identify HKL as a natural-origin antibiotic potentiator that enhances the efficacy of low-dose SMM-Na against AHPND-causing\n                    <jats:italic>V.\u00a0parahaemolyticus<\/jats:italic>\n                    . These findings provide proof-of-concept evidence for a dose-sparing combination strategy that may reduce therapeutic SMM-Na input while supporting pathogen control and host recovery in shrimp aquaculture.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1882728","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:25:44Z","timestamp":1782793544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Honokiol potentiates low-dose sulfamonomethoxine sodium against antimicrobial-resistant AHPND-causing Vibrio parahaemolyticus through bacterial membrane disruption and host recovery"],"prefix":"10.3389","volume":"17","author":[{"given":"Yihuan","family":"Chen","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University","place":["Ningbo, China"]},{"name":"Key Laboratory of Aquacultural Biotechnology of 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Molecular Biology, School of Marine Sciences, Ningbo University","place":["Ningbo, China"]},{"name":"Key Laboratory of Aquacultural Biotechnology of Ministry of Education, Ningbo University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Mariculture Research Institute, Zhejiang Key Laboratory of Coastal Biological Germplasm Resources Conservation and Utilization","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Mariculture Research Institute, Zhejiang Key Laboratory of Coastal Biological Germplasm Resources Conservation and Utilization","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Shang","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular 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