多酚干扰细菌群体感应研究进展<sup>*</sup>

doi:10.13523/j.cb.2203017

中国生物工程杂志

2022, Vol. 42

Issue (9): 93-104 DOI: 10.13523/j.cb.2203017

综述

多酚干扰细菌群体感应研究进展^*

王满满^1,²,吴胜波^1,²,吴昊³,张鹏^1,²,张育淼¹,乔建军^1,^2,^3,⁴,财音青格乐^1,^2,^***(

)

1.天津大学化工学院天津 300072
2.天津大学系统生物工程教育部重点实验室天津 300072
3.天津大学浙江绍兴研究院绍兴 312300
4.天津化学化工协同创新中心合成生物学平台天津 300072

Research Progress on Polyphenol-based Quorum Sensing Interfering

WANG Man-man^1,²,WU Sheng-bo^1,²,WU Hao³,ZHANG Peng^1,²,ZHANG Yu-miao¹,QIAO Jian-jun^1,^2,^3,⁴,CAIYIN Qing-ge-le^1,^2,^***(

)

1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2. Key Laboratory of Systems Bioengineering of Ministry of Education, Tianjin University, Tianjin 300072, China
3. Zhejiang Shaoxing Research Institute of Tianjin University, Shaoxing 312300, China
4. Synthetic Biology Research Platform, Tianjin Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China

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摘要：

多酚化合物是人类日常饮食中一类典型的天然产物,具有干扰分子信号通路、影响肠道菌群组成和保护人体肠道健康的功能。针对不同微生物群体感应(quorum sensing,QS)系统,多酚能够干扰细菌生物膜的形成和微生物致病性。介绍多酚的类型、来源和含量,总结多酚对多种QS相关表型,如菌体运动性、黏附性、生物膜形成和毒力因子的释放等具有的干扰作用,以及一些常见多酚对典型病原体的干扰作用,提出基于多酚的QS干扰在未来疾病治疗中面临的主要挑战。

关键词： 耐药性; 群体感应干扰; 多酚化合物; 生物膜

Abstract:

Polyphenols, a typical class of natural products in our daily diet, have functions of interfering with molecular signaling pathways, affecting the composition of gut microbiota, and protecting human health. Biofilm formation and microbial pathogenicity can be interfered by various polyphenols targeting different microbial quorum sensing (QS) systems, which provides a theoretical basis for the clinical applications of polyphenols. However, the complexity of polyphenol-based interference involves multifarious compounds, various microorganisms and intricate microbial phenotypes. First, a brief summary of types, sources, and amounts of polyphenols is introduced, including flavonoids, phenolic acids, stilbene, lignans, and others based on the number of phenolic rings and structural elements. Then the polyphenol-based interference targeting diverse QS-relevant phenotypes is summarized, including microbial motility, microbial adhesion, biofilm formation, and the release of virulence factors. Furthermore, various interference effects of some common polyphenols on the typical pathogens are summarized to contribute to potential applications. Finally, some key challenges and general perspectives on polyphenol-based interference for various future therapeutic applications are identified.

Key words: Antibiotic resistance Quorum sensing interference Polyphenols Biofilm

收稿日期: 2022-03-08 出版日期: 2022-10-10

ZTFLH:

Q93

基金资助: * 国家重点研发计划(2019YFA0905600);国家重点研发计划(2020YFA0906800);国家重点研发计划(2020YFA0907900);国家自然科学基金(32070073);中国创新研究群体基金(21621004)

通讯作者: 财音青格乐 E-mail: qinggele@tju.edu.cn

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引用本文:

王满满,吴胜波,吴昊,张鹏,张育淼,乔建军,财音青格乐. 多酚干扰细菌群体感应研究进展^*[J]. 中国生物工程杂志, 2022, 42(9): 93-104.

WANG Man-man,WU Sheng-bo,WU Hao,ZHANG Peng,ZHANG Yu-miao,QIAO Jian-jun,CAIYIN Qing-ge-le. Research Progress on Polyphenol-based Quorum Sensing Interfering. China Biotechnology, 2022, 42(9): 93-104.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2203017 或 https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I9/93

分类	亚类	典型分子	来源	含量	参考文献
黄酮类	黄酮醇	槲皮素、山柰酚、杨梅素、异鼠李素	浆果、蔬菜、茶、葡萄酒	120 mg/100g洋葱、5.73 mg/100 g浆果	[25,43]
	黄烷醇	(+)-儿茶素、(+)-表儿茶素	水果、红酒、绿茶、可可制品、谷物	25 mg/100 g杏仁、30 mg/100 mL红酒	[25,44]
	黄烷酮	柚皮素、柚皮苷、橙皮素、橙皮苷	柑橘类水果、果汁	35~147 mg/100 g橙子、18~74 mg/100 mL柑橘类果汁	[45⇓-47]
	黄酮	芹菜素、木犀草素	茶、干草药、果汁、葡萄酒、蔬菜、谷物	5 320 mg/100 g洋甘菊、1 350 mg/100 g欧芹叶、15~35 mg/100 g小米	[48]
	异黄酮	葛根素、大豆素	大豆及其制品	58~380 mg/100 g大豆、3~17 mg/100 mL豆乳	[25,49]
	花青素	矢车菊色素、锦葵色素、葡萄皮红色素	水果、谷物、葡萄酒、蔬菜	200~400 mg/100 g黑加仑或黑莓、200~35 mg/100 mL葡萄酒、72 mg/100 mL红酒	[25,50]
酚酸类	羟基苯甲酸	儿茶酸、没食子酸、丁香酸、水杨酸	菊科香料、草本植物	73~108 mg/100 g大茴香、346~907 mg/100 g栗子	[24,51]
	羟基肉桂酸	对香豆酸、咖啡酸、阿魏酸、绿原酸、奎尼酸	咖啡、茶、葡萄酒、可可、水果、蔬菜和谷物	147 mg/100 g蓝莓、87 mg/100 g咖啡、6~140 mg/L葡萄	[24 48-52]
芪类	-	白藜芦醇	花生、葡萄酒、水果	1.5~2.2 mg/100 mL葡萄酒	[25,53]
木脂素类	经典木脂素	亚麻木脂素、芝麻素、丁香树脂醇	亚麻籽、谷物、水果、蔬菜、豆科植物	370 mg/100 g亚麻籽	[25]
	新木质素	厚朴酚、和厚朴酚、异厚朴酚、厚朴新酚	不同植物,如玉兰树的根	-	[54]
其他	酪醇	酪醇、羟基酪醇、橄榄多酚、川芎甙	啤酒、葡萄酒、橄榄油	5.73 mg/100 mL雪莉酒、 14.42 mg/100 g橄榄	[37]
	烷基酚	4-乙基苯酚、4-乙烯基苯酚、4-乙基邻苯二酚、4-甲基邻苯二酚	啤酒、咖啡	0.13 mg/100 mL咖啡	[37]

表1 常见多酚的分类、结构和来源

图1 微生物膜的形成过程及潜在干扰因素

图2 P. aeruginosa QS系统调控胞外多糖及毒力因子生产的机制

多酚	CID	浓度/ (μg·mL^-1)	细菌	生理活性干扰	效果	参考文献
丁香酚	3 314	0.05	EHEC	生物膜的形成和菌体运动性	↓	[75⇓-77]
		0.05	EHEC	菌毛、纤维素、运动性和QS相关基因	↓
		0.05	E. coli K-12	卷曲菌毛的产生	↓
		0.4	MRSA	生物膜的形成和细胞渗透性	↓
		0.1	MRSA	生物膜和肠毒素相关基因	↓
		66	P. aeruginosa PAO1	生物膜的形成	↓
		33	P. aeruginosa PAO1	菌体运动性	↓
		66	P. aeruginosa PAO1	las和pqs系统相关基因	↓
		25	C. violaceum CV026	紫色杆菌素的产生	↓
		8	P. aeruginosa PAO1	绿脓菌素的产生	↓
		33	P. aeruginosa PAO1	弹性蛋白酶的产生	↓
香芹酚	10 364	150	E. coli O157:H7	鞭毛蛋白的合成	↓	[6,56 -57
		150	E. coli O157:H7	菌体运动性	↓	[78-79]
		60	S. Typhimurium DT104	菌体运动性	↓
		75	S. Typhimurium DT104	对猪上皮细胞的侵袭能力	↓
		15	C. violaceum ATCC 12472	生物膜的形成	↓
		113	S. Typhimurium DT104	生物膜的形成	↓
		75	S. aureus 0074	生物膜的形成	↓
		15	C. violaceum	紫色杆菌素的产生	↓
		30	C. violaceum	几丁质酶活性	↓
		64	Escherichia cloaca C4	生物膜、菌毛和EPS的表达	↓
		32	E. cloaca C4	菌体运动性	↓
		64	E. cloaca C4	胞外多糖和生物膜的产生	↓
		25	S. mutans ATCC 25175	自溶素和超氧化物歧化酶的表达	↑
没食子酸	370	1 000	P. aeruginosaATCC 10145	菌体运动性和黏附性	↓	[80-81]
		1 000	S. aureus CECT 976	菌体运动性和黏附性	↓
		1 000	S. aureus CECT 976	生物膜的形成	↓
		1 000	L. monocytogenes ATCC 15313	菌体运动性和黏附性	↓
		1 000	L. monocytogenes ATCC 15313	生物膜的形成	↓
		1 000	E. coli CECT434	菌体运动性	↓
		1 000	E. coli CECT434	生物膜的形成	↓
香豆素	323	200	P. aeruginosa	AHL介导的QS系统相关基因	↓	[82⇓⇓-85]
		200	P. aeruginosa PAO1	las、rhl和pqs系统相关基因	↓
		200	P. aeruginosa PA14	生物膜的形成和菌体运动性	↓
		200	P. aeruginosa PA14	吩嗪的产生	↓
		200	Burkholderia cepacia NCTC10743	蛋白酶活性	↓
		200	Aliivibrio fischeri MJ11	生物发光	↓
		365	S. typhimurium ATCC 14028	生物膜、菌毛和纤维素的产生	↓
多酚	CID	浓度/ (μg·mL^-1)	细菌	生理活性干扰	效果	参考文献
		365	S. typhimurium ATCC 14028	生物膜相关基因	↓
		365	S. typhimurium ATCC 14028	菌体运动性	↓
		292	P. aeruginosa	绿脓菌素和蛋白酶的产生	↓
		100	S. aureus MTCC 96	生物膜的形成和菌体运动性	↓
表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)	65 064	275	Gram-negative bacteria	C4-、C6-、和C10-HSLs介导的生物膜和EPS的形成	↓	[86⇓⇓-89]
		275	Gram-negative bacteria	C4-、C6-、和C10-HSLs介导的表型	↓
		0.1	P. aeruginosa	淀粉样纤维的结构重塑	↑
		0.1	P. aeruginosa	QS系统相关基因	↓
		20	L. monocytogenes ATCC 19114	生物膜的形成和菌体运动性	↓
		40	L. monocytogenes ATCC 19114	溶血活性	↓
		40	L. monocytogenes ATCC 19114	QS和毒力因子相关基因	↓
		250	Shewanella baltica XH2	生物膜的形成	↓
		250	S. baltica XH2	菌体运动性	↓
		250	S. baltica XH2	外切酶和信号分子的活性	↓
		250	S. baltica XH2	QS系统相关基因	↓
		250	S. baltica XH2	AI-2和胞外多糖的产生	↓
姜黄素	1 794 427	150	Gram-negative bacteria	C4-和C6-HSLs介导的生物膜和EPS 的形成	↓	[69,86 90⇓⇓-93]
		150	Gram-negative bacteria	C4-和C6-HSLs介导的表型	↓
		2	P. aeruginosa PAO1	生物膜的形成	↓
		1.5	P. aeruginosa PAO1	绿脓菌素的产生	↓
		3	P. aeruginosa PAO1	蛋白酶活性和菌体运动性	↓
		1	P. aeruginosa PAO1	弹性蛋白酶活性	↓
		1	P. aeruginosa PAO1	信号分子的浓度	↓
		1~3	P. aeruginosa PAO1	QS系统相关基因	↓
		25	V. harveyi MTCC3438	生物发光	↓
		100	Vibrio	菌体运动性	↓
		50	Vibrio	生物膜的形成	↓
		25	Vibrio	胞外多糖和藻酸盐的产生	↓
		5	Vibrio	β-半乳糖苷酶和蛋白酶活性	↓
		25	C. violaceum	QS系统产物	↓
		25	Serratia marcescens FJ584421	QS系统产物	↓
		100	E. coli ATCC10536	生物膜的形成	↓
		3.7	S. mutans	生物膜的形成	↓
白藜芦醇	445 858	100	MRSA	生物膜的形成	↓	[70-71 ,74,94-95]
		100	MRSA	QS、表面和分泌蛋白、荚膜多糖相关基因的表达	↓
多酚	CID	浓度/ (μg·mL^-1)	细菌	生理活性干扰	效果	参考文献
		68	P. aeruginosa PAO1	绿脓菌素的产生	↓
		23	P. aeruginosa PAO1	菌体运动性	↓
		10	C. violaceum CV026	紫色杆菌素的产生	↓
		20	Yersinia enterocolitica CECT4315 CECT494;Erwinia carotovora CECT225 and C. violaceum	AHL的浓度	↓

表2 多酚对各种微生物表型的干扰

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