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We synthesized 54 garlic-derived disulfides and identified compound b as the most potent candidate (EC50 = 2.85 \u03bcg\/mL), which significantly surpassed allicin and zhongshengmycin (ZSM). In planta assays on Cuiguan pear demonstrated that b provided exceptional curative and protective efficacy, effectively suppressing fire blight infections in flowers, leaves, shoots, and fruits. Mechanistically, b triggered lethal ROS accumulation by inhibiting catalase (CAT) and superoxide dismutase (SOD) activities, leading to compromised cell envelope and ultrastructural damage in E. amylovora. Notably, b attenuated bacterial virulence by suppressing swimming and swarming motility, reducing biofilm formation, and decreasing extracellular cellulase activity, while also inhibiting DNA and protein biosynthesis. Additionally, b exhibited minimal toxicity toward nontarget organisms, such as silkworms (Bombyx mori) and earthworms (Eisenia fetida), highlighting its environmental safety. These findings establish compound b as a highly effective, safe, and eco-friendly candidate for sustainable fire blight management.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05183","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:56:31Z","timestamp":1780671391000},"page":"17875-17885","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis,\nAntibacterial Evaluation, and Mechanistic\nInsights of Garlic-Derived Disulfides against\n                    <i>Erwinia amylovora<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Wanjun","family":"Li","sequence":"first","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wei","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"Jiangxi Science & Technology Normal University , , ,","place":["Nanchang, China, 330013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlong","family":"Liu","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangye","family":"Chen","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Hangzhou Beicaoyuan Ecological Agriculture Co., Ltd ., ,","place":["Hangzhou, China, 311113"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zeng","sequence":"additional","affiliation":[{"name":"The Connecticut Agricultural Experiment Station , , , ,","place":["New Haven, Connecticut, United States, 06511"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-8735","authenticated-orcid":true,"given":"Zi-Ning","family":"Cui","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"issue":"4","key":"2026073021192975400_cit1","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/S2095-3119(18)62033-7","article-title":"Fire blight disease, a fast-approaching\nthreat to apple and pear production in china","volume":"18","author":"Zhao","year":"2019","journal-title":"J. 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Plant Pathol."},{"issue":"1","key":"2026073021192975400_cit5","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1146\/annurev.phyto.36.1.227","article-title":"Management\nof fire blight: a case study in microbial\necology","volume":"36","author":"Johnson","year":"1998","journal-title":"Annu. Rev. Phytopathol."},{"issue":"1","key":"2026073021192975400_cit6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1080\/15538362.2017.1377670","article-title":"Health status of\nthe pear tree following the establishment of fire blight in northern\nTunisia","volume":"18","author":"Gaaliche","year":"2018","journal-title":"Int. J. Fruit Sci."},{"issue":"9","key":"2026073021192975400_cit7","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1111\/mpp.12436","article-title":"Bacterial\ndisease management: challenges, experience, innovation and future\nprospects: challenges in bacterial molecular plant pathology","volume":"17","author":"Sundin","year":"2016","journal-title":"Mol. Plant Pathol."},{"key":"2026073021192975400_cit8","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1146\/annurev.phyto.40.120301.093927","article-title":"Antibiotic use in\nplant agriculture","volume":"40","author":"McManus","year":"2002","journal-title":"Annu. Rev. Phytopathol."},{"issue":"4","key":"2026073021192975400_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2024.110044","article-title":"Application\nof inhibitors targeting\nthe type III secretion system in phytopathogenic bacteria","volume":"36","author":"He","year":"2025","journal-title":"Chin. Chem. 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Plant\nPathol."},{"issue":"2","key":"2026073021192975400_cit25","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/j.1364-3703.2011.00738.x","article-title":"Genetic\ncharacterization of the HrpL regulon of the fire blight pathogen Erwinia amylovora reveals novel virulence factors","volume":"13","author":"Mcnally","year":"2012","journal-title":"Mol. Plant Pathol."},{"issue":"43","key":"2026073021192975400_cit26","doi-asserted-by":"publisher","first-page":"15971","DOI":"10.1021\/acs.jafc.3c05212","article-title":"Innovative\nstrategy for the control of citrus canker:\ninhibitors targeting the type III secretion system of Xanthomonas citri subsp. citri","volume":"71","author":"Wang","year":"2023","journal-title":"J. Agric. 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Sci."},{"issue":"22","key":"2026073021192975400_cit34","doi-asserted-by":"publisher","first-page":"12434","DOI":"10.1021\/acs.jafc.3c09928","article-title":"Design, synthesis,\nand antibacterial evaluation of novel isoindolin-1-ones\nderivatives containing piperidine fragments","volume":"72","author":"Zheng","year":"2024","journal-title":"J. Agric. 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