{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:47:09Z","timestamp":1761198429098,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"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":"publisher","award":["22206166"],"award-info":[{"award-number":["22206166"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: Due to the widespread use of broad-spectrum antibiotics, the problem of antibiotic resistance has become an increasingly serious global threat. One of the key mechanisms of Escherichia coli resistance to beta-lactam antibiotics is the production of beta-lactamase enzymes, which poses a dilemma for clinicians in selecting antibiotics when faced with resistant bacterial infections. However, research on the reversal of bacterial resistance is limited. Methods: This study involved the preparation of Iris tectorum extract and detection of its effects on antibiotics sensitivity, extended-spectrum beta-lactamase (ESBL) gene expression, and histidine kinase phosphorylation levels in \u03b2-lactam antibiotic-resistant Escherichia coli. Additionally, analyses of the active ingredients of Iris tectorum extract were conducted with a liquid chromatography\u2013mass spectrometer, and the binding sites were predicted by molecular docking. Results: Iris tectorum extract could restore the sensitivity of Escherichia coli to beta-lactam antibiotics and reduce the expression levels of ESBL genes and histidine phosphorylation levels. The active ingredients of Iris tectorum extract may be irigenin and tectorigenin, and these two small molecules could bind to histidine kinase to inhibit phosphorylation. Conclusions: Iris tectorum extract may serve as an antibiotic adjuvant, restoring the sensitivity of antibiotic-resistant bacteria by inhibiting histidine kinase phosphorylation, thereby alleviating the problem of Escherichia coli resistance to \u03b2-lactam antibiotics.<\/jats:p>","DOI":"10.3390\/molecules30030663","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T12:18:56Z","timestamp":1738585136000},"page":"663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Small Molecules from Medicinal Plant Iris tectorum as Histidine Kinase Inhibitor to Resensitize \u03b2-Lactam-Resistant Escherichia coli"],"prefix":"10.3390","volume":"30","author":[{"given":"Youqi","family":"Ji","sequence":"first","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinhuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhangkai","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danlei","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhendi","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyi","family":"Shao","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5348-4497","authenticated-orcid":false,"given":"Xin","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Green Pharmaceutical Collaborative Innovation Center, School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6820-4593","authenticated-orcid":false,"given":"Zishu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-2817","authenticated-orcid":false,"given":"Dongqing","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,3]]},"reference":[{"key":"ref_1","first-page":"237","article-title":"History of Antibiotics Research","volume":"398","author":"Mohr","year":"2016","journal-title":"Curr. 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