关键词: ABC transporter ATP-binding protein Cutibacterium acnes NADH-quinone oxidoreductase Oleum cinnamomi antibacterial covalently modifies metabolomics

Mesh : Anti-Bacterial Agents / pharmacology chemistry Microbial Sensitivity Tests Propionibacteriaceae / drug effects Plant Extracts / pharmacology chemistry Proteomics / methods Acrolein / analogs & derivatives pharmacology chemistry Metabolomics / methods

来  源:   DOI:10.3390/molecules29133165   PDF(Pubmed)

Abstract:
Oleum cinnamomi (OCM) is a volatile component of the Cinnamomum cassia Presl in the Lauraceae family, which displays broad-spectrum antibacterial properties. It has been found that OCM has a significant inhibitory effect against Cutibacterium acnes (C. acnes), but the precise target and molecular mechanism are still not fully understood. In this study, the antibacterial activity of OCM against C. acnes and its potential effect on cell membranes were elucidated. Metabolomics methods were used to reveal metabolic pathways, and proteomics was used to explore the targets of OCM inhibiting C. acnes. The yield of the OCM was 3.3% (w/w). A total of 19 compounds were identified, representing 96.213% of the total OCM composition, with the major constituents being phenylpropanoids (36.84%), sesquiterpenoids (26.32%), and monoterpenoids (15.79%). The main component identified was trans-cinnamaldehyde (85.308%). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of OCM on C. acnes were 60 µg/mL and 180 µg/mL, respectively. The modified proteomics results indicate that cinnamaldehyde was the main bioactive ingredient within OCM, which covalently modifies the ABC transporter adenosine triphosphate (ATP)-binding protein and nicotinamide adenine dinucleotide (NADH)-quinone oxidoreductase, hindering the amino acid transport process, and disrupting the balance between NADH and nicotinamide adenine dinucleoside phosphorus (NAD+), thereby hindering energy metabolism. We have reported for the first time that OCM exerts an antibacterial effect by covalent binding of cinnamaldehyde to target proteins, providing potential and interesting targets to explore new control strategies for gram-positive anaerobic bacteria.
摘要:
肉桂(OCM)是月桂科中肉桂的挥发性成分,具有广谱抗菌性能。已发现OCM对痤疮皮肤有显着的抑制作用(C.痤疮),但是精确的靶标和分子机制仍然没有完全理解。在这项研究中,阐明了OCM对痤疮丙酸杆菌的抗菌活性及其对细胞膜的潜在作用。代谢组学方法用于揭示代谢途径,并利用蛋白质组学方法探索OCM抑制痤疮丙酸杆菌的作用靶点。OCM的产率为3.3%(w/w)。共鉴定出19个化合物,占总OCM成分的96.213%,主要成分为苯丙素类化合物(36.84%),倍半萜(26.32%),和单萜(15.79%)。主要成分为反式肉桂醛(85.308%)。OCM对痤疮梭菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)分别为60µg/mL和180µg/mL,分别。修饰的蛋白质组学结果表明,肉桂醛是OCM中的主要生物活性成分,共价修饰ABC转运蛋白三磷酸腺苷(ATP)结合蛋白和烟酰胺腺嘌呤二核苷酸(NADH)-醌氧化还原酶,阻碍了氨基酸的运输过程,破坏NADH与烟酰胺腺嘌呤二核苷磷(NAD+)的平衡,从而阻碍能量代谢。我们首次报道了OCM通过肉桂醛与靶蛋白共价结合发挥抗菌作用,提供潜在和有趣的靶标,以探索革兰氏阳性厌氧菌的新控制策略。
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