Wang Lihan, Li Shihang, Liu Jingxun, Qi Xuehe, Cheng Jingqi, Guo Ling, Yang Xinyan, Jiang Yujun
Key Lab of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China.
Key Lab of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Cattle and Sheep Milk and Meat Products Risk Control and Key Technology, State Administration for Market Regulation, Hohhot 010100, China.
Int J Food Microbiol. 2025 Nov 2;442:111381. doi: 10.1016/j.ijfoodmicro.2025.111381. Epub 2025 Aug 5.
Bacillus cereus (B. cereus) is a food-borne pathogen that produces proteases in raw milk, causing dairy products to deteriorate in quality through protein precipitation and bitterness. Quorum sensing (QS) is a bacterial communication mechanism where autoinducers (AI) are produced and accumulated to regulate gene expression, including that of extracellular enzymes. In this study, curcumin could act as a natural QS inhibitor (QSI), hindering the AI -2 production and reducing proteolytic activity. Whole genome sequencing results showed that B. cereus D8 contained luxS and other genes related to the transport of AI-2, indicating that the LuxS/AI-2 QS system regulated physiological activity. In addition, the presence of nprB demonstrated the protease-producing ability of B. cereus D8. Transcriptome and molecular docking analyses revealed that curcumin may bind to LuxS, leading to upregulation of the luxS gene for AI-2 synthesis and downregulation of the lsrK, lsrA, and lsrR genes involved in AI-2 transport. Curcumin addition also led to the inhibition of various physiological activities of B. cereus D8 including biosynthesis of various amino acids, as well as the downregulation of nprB gene expression, thereby reducing protease production. The exogenous addition of AI-2 also confirmed that curcumin did not alter the expression of luxS gene and upregulated lsrK, lsrR, and nprB genes, indicating that curcumin did not degrade AI-2. This study reveals the molecular mechanism that curcumin inhibited protease production in B. cereus by regulating the LuxS/AI-2 QS system, providing a theoretical basis for biological inhibitor development.
蜡样芽孢杆菌是一种食源性病原体，它在生牛奶中产生蛋白酶，通过蛋白质沉淀和苦味导致乳制品质量下降。群体感应（QS）是一种细菌通讯机制，其中自诱导物（AI）产生并积累以调节基因表达，包括细胞外酶的基因表达。在本研究中，姜黄素可作为一种天然的群体感应抑制剂（QSI），阻碍AI-2的产生并降低蛋白水解活性。全基因组测序结果表明，蜡样芽孢杆菌D8含有luxS和其他与AI-2转运相关的基因，表明LuxS/AI-2群体感应系统调节生理活性。此外，nprB的存在证明了蜡样芽孢杆菌D8的产蛋白酶能力。转录组和分子对接分析表明，姜黄素可能与LuxS结合，导致参与AI-2合成的luxS基因上调，以及参与AI-2转运的lsrK、lsrA和lsrR基因下调。添加姜黄素还导致蜡样芽孢杆菌D8的各种生理活性受到抑制，包括各种氨基酸的生物合成，以及nprB基因表达的下调，从而减少蛋白酶的产生。外源添加AI-2也证实，姜黄素不会改变luxS基因的表达，而是上调lsrK、lsrR和nprB基因，表明姜黄素不会降解AI-2。本研究揭示了姜黄素通过调节LuxS/AI-2群体感应系统抑制蜡样芽孢杆菌中蛋白酶产生的分子机制，为生物抑制剂的开发提供了理论依据。
