{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:33Z","timestamp":1787372853077,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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":["32172749"],"award-info":[{"award-number":["32172749"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32172749"],"award-info":[{"award-number":["32172749"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Itaconic acid has been reported to possess anti-inflammatory and antibacterial properties. However, its specific mechanisms of action against pathogenic bacteria, especially in the context of purine metabolism, remain poorly understood. Here, we investigate the impact of itaconic acid on the purine metabolism of PCN033, a highly pathogenic porcine extraintestinal pathogenic Escherichia coli (ExPEC) strain. Our in vitro and in vivo experiments demonstrated that itaconic acid significantly inhibited the proliferation of PCN033. Multi-omics analyses, including transcriptome and metabolome sequencing, revealed that itaconic acid severely disrupted the purine metabolism pathway of PCN033. Further mechanistic studies identified PRPP amidotransferase (PurF), a key enzyme in de novo purine synthesis, as a direct target of itaconic acid. Molecular docking and click chemistry experiments provided compelling evidence that itaconic acid specifically binds to the second cysteine residue (2C) of PurF, leading to the inhibition of its enzymatic activity. These data reveal a novel and critical mechanism by which itaconic acid exerts its antibacterial effects in response to bacterial infection. Importantly, our in vivo data show that supplementation with itaconic acid alleviated weight loss, organ damage, and inflammatory responses induced by PCN033 infection in mice and nursery pigs. These novel findings enhance our understanding of the antibacterial mechanisms of itaconic acid. Supplementation with itaconic acid could serve as a therapeutic strategy for treating pathogenic bacterial infections in humans and other animals.<\/jats:p>","DOI":"10.3390\/microorganisms14081852","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:10:20Z","timestamp":1787213420000},"page":"1852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Itaconic Acid Directly Binds to the Cysteine Residue of PurF: A Novel Mechanism for Inhibiting Purine Metabolism in Porcine Pathogenic Escherichia coli"],"prefix":"10.3390","volume":"14","author":[{"given":"Haozhen","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlong","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00135-18","DOI":"10.1128\/CMR.00135-18","article-title":"Global Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages","volume":"32","author":"Manges","year":"2019","journal-title":"Clin. 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