{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:12:20Z","timestamp":1787501540248,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"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":"crossref","award":["32170130"],"award-info":[{"award-number":["32170130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Salmonella\u00a0Typhimurium, a significant intracellular foodborne pathogen, regulates host cell autophagy to achieve its own survival by injecting effector proteins into host cells via its type III secretion system (T3SS). Berberine hydrochloride (BH), an isoquinoline alkaloid derived from medicinal plants such as Coptis chinensis, has demonstrated potential antibacterial and immunomodulatory properties. However, the mechanisms by which BH combats S. Typhimurium by enhancing host autophagic flux through the inhibition of the type III secretion system remain to be fully elucidated. Here, we found that BH disrupts biofilm formation of S. Typhimurium, significantly inhibits the expression of genes associated with T3SS, and robustly enhances autophagy activity in macrophages infected with the pathogen. In a mouse model (C57BL\/6 female 20 \u00b1 1 g\/mouse), BH significantly improved survival rates, reduced bacterial loads in tissues, and alleviated pathological damage. Molecular docking studies revealed that BH binds to key T3SS proteins, including SipB, SseA, and SsrB. These findings indicate that BH holds promise as a potentially effective therapeutic strategy for combating S. Typhimurium infections.<\/jats:p>","DOI":"10.3390\/biom15111589","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"1589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Berberine Hydrochloride Reduces the Intracellular Survival of Salmonella Typhimurium by Enhancing Host Autophagic Flux Through the Inhibition of the Type III Secretion System"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1449-2655","authenticated-orcid":false,"given":"Jianan","family":"Huang","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Lu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidi","family":"Chen","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-8887","authenticated-orcid":false,"given":"Xihui","family":"Shen","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qadir","family":"Bakhsh","sequence":"additional","affiliation":[{"name":"Institute of Plant Sciences, University of Sindh, Jamshoro 76080, Sindh, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofu","family":"Qin","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.chom.2017.03.009","article-title":"Salmonella Typhimurium Diarrhea Reveals Basic Principles of Enteropathogen Infection and Disease-Promoted DNA Exchange","volume":"21","author":"Wotzka","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4161\/viru.21087","article-title":"Salmonella Enterica Serovars Typhimurium and Typhi as Model Organisms: Revealing Paradigm of Host-Pathogen Interactions","volume":"3","author":"Garai","year":"2012","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41579-021-00561-4","article-title":"Salmonella Typhimurium and Inflammation: A Pathogen-Centric Affair","volume":"19","year":"2021","journal-title":"Nat. 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