School Life and Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry Education, State Key Laboratory of Marine Resource Utilization in South China Sea, Hainan University, Haikou, 570228, China.
School of Food (Biological) Engineering, Xuzhou University of Technology, Xuzhou, 221000, China.
Appl Microbiol Biotechnol. 2020 Jun;104(11):5025-5037. doi: 10.1007/s00253-020-10593-0. Epub 2020 Apr 4.
Chromobacterium violaceum, one free-living Gram-negative bacterium, is abundantly presented in tropics and sub-tropics soil and aquatic environment; it is also an opportunistic human pathogen. Here, two cinnamic acid derivatives, i.e., 4-dimethylaminocinnamic acid (DCA) and 4-methoxycinnamic acid (MCA), were identified as potential quorum sensing (QS) and biofilm inhibitors in C. violaceum ATCC12472. Both DCA (100 μg/mL) and MCA (200 μg/mL) inhibited the levels of N-decanoyl-homoserine lactone (C10-HSL) and reduced the production of certain virulence factors in C. violaceum, including violacein, hemolysin, and chitinase. Metabolomics analysis indicated that QS-related metabolites, such as ethanolamine and L-methionine, were down-regulated after treatment with DCA and MCA. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that DCA and MCA markedly suppressed the expression of two QS-related genes (cviI and cviR). In addition, DCA and MCA also inhibited biofilm formation and enhanced the susceptibility of biofilms to tobramycin, which was evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Our results indicated that DCA and MCA can serve as QS-based agent for controlling pathogens.Key Points • DCA and MCA inhibited QS and biofilm formation in C. violaceum.• The combination of DCA or MCA and tobramycin removed the preformed biofilm of C. violaceum. • DCA or MCA inhibited virulence factors and expressions of cviI and cviR of C. violaceum.• DCA or MCA are potential antibiotic accelerants for treating C. violaceum infection.
类铜绿假单胞菌是一种自由生活的革兰氏阴性菌，大量存在于热带和亚热带土壤和水生环境中；它也是一种机会性病原体。在这里，两种肉桂酸衍生物，即 4-二甲氨基肉桂酸（DCA）和 4-甲氧基肉桂酸（MCA），被鉴定为铜绿假单胞菌 ATCC12472 中的潜在群体感应（QS）和生物膜抑制剂。DCA（100μg/mL）和 MCA（200μg/mL）均抑制了 N-癸酰基高丝氨酸内酯（C10-HSL）的水平，并降低了铜绿假单胞菌某些毒力因子的产生，包括紫质、溶血素和几丁质酶。代谢组学分析表明，DCA 和 MCA 处理后，QS 相关代谢物，如乙醇胺和 L-蛋氨酸，下调。定量实时聚合酶链反应（qRT-PCR）表明，DCA 和 MCA 显著抑制了两个 QS 相关基因（cviI 和 cviR）的表达。此外，DCA 和 MCA 还抑制生物膜形成，并增强生物膜对妥布霉素的敏感性，这可以通过扫描电子显微镜（SEM）和共聚焦激光扫描显微镜（CLSM）得到证明。我们的结果表明，DCA 和 MCA 可以作为基于 QS 的药物来控制病原体。
关键点
• DCA 和 MCA 抑制铜绿假单胞菌的 QS 和生物膜形成。
• DCA 或 MCA 与妥布霉素联合使用可去除铜绿假单胞菌的预形成生物膜。
• DCA 或 MCA 抑制铜绿假单胞菌的毒力因子和 cviI 和 cviR 的表达。
• DCA 或 MCA 是治疗铜绿假单胞菌感染的潜在抗生素加速剂。
