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Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle.
Xie, L Y; Xu, Y B; Ding, X Q; Liang, S; Li, D L; Fu, A K; Zhan, X A.
Afiliación
  • Xie LY; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Xu YB; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Ding XQ; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Liang S; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Li DL; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Fu AK; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China.
  • Zhan XA; Key Laboratory of Animal Nutrition and Feed in East China, Ministry of Agriculture and Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Feed Science Institute, College of Animal Science, Zhejiang University, Hangzhou 310058, China. Electronic address: xazan@zju.edu.cn.
Biomed Pharmacother ; 167: 115487, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37713987
Itaconic acid (IA), a metabolite generated by the tricarboxylic acid (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions in intracellular environments. Previous studies suggested that IA and DI only inhibit bacterial growth in carbon-limited environments; however, whether IA and DI maintain antibacterial activity in carbon-enriched environments remains unknown. Here, IA and DI inhibited the bacteria with minimum inhibitory concentrations of 24.02 mM and 39.52 mM, respectively, in a carbon-enriched environment. The reduced bacterial pathogenicity was reflected in cell membrane integrity, motility, biofilm formation, AI-2/luxS, and virulence. Mechanistically, succinate dehydrogenase (SDH) activity and fumaric acid levels decreased in the IA and DI treatments, while isocitrate lyase (ICL) activity was upregulated. Inhibited TCA circulation was also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism and lysine degradation were suppressed. In summary, these results indicated that IA and DI reduced bacterial pathogenicity while exerting antibacterial functions by inhibiting TCA circulation. This study enriches knowledge on the inhibition of bacteria by IA and DI in a carbon-mixed environment, suggesting an alternative method for treating bacterial infections by immune metabolites.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomed Pharmacother Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomed Pharmacother Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia