咖啡酸对铜绿假单胞菌群体感应抑制探究

宋文旭; 冯玉琦; 韩啸枫; 王世伟; 徐翠香; 张海祥; 沈立新

doi:10.16152/j.cnki.xdxbzr.2024-05-009

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咖啡酸对铜绿假单胞菌群体感应抑制探究

西北大学生物学科办学100周年专刊 | 更新时间：2024-09-30

- 咖啡酸对铜绿假单胞菌群体感应抑制探究
- The inhibitory effect of caffeic acid on Pseudomonas aeruginosa QS system and its target
- 西北大学学报（自然科学版） 2024年54卷第5期页码：867-875
- 作者机构：
  
  1.西北大学　生命科学学院，陕西　西安　710069
  2.陕西省人民医院　陕西省感染与免疫疾病重点实验室，陕西　西安　710068
- 作者简介：
  
  宋文旭，女，从事群体感应抑制剂开发相关研究，songwenxu@stumail.nwu.edu.cn。
  沈立新，女，博士，教授，从事病原微生物致病及耐药机制等研究，shenlx@nwu.edu.cn。
- 基金信息：
  
  陕西省自然科学基金(2018ZDXM-SF-004);陕西化生基础科学研究项目(22JHZ008);陕西省感染与免疫疾病重点实验室开放基金(2023-KFZD-3)
- DOI：10.16152/j.cnki.xdxbzr.2024-05-009
  中图分类号： R378
- 纸质出版日期：2024-10-25，
  
  收稿日期：2024-08-08，
- 稿件说明：
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宋文旭, 冯玉琦, 韩啸枫, 等. 咖啡酸对铜绿假单胞菌群体感应抑制探究[J]. 西北大学学报（自然科学版）, 2024,54(5):867-875.

SONG Wenxu, FENG Yuqi, HAN Xiaofeng, et al. The inhibitory effect of caffeic acid on Pseudomonas aeruginosa QS system and its target[J]. Journal of Northwest University (Natural Science Edition), 2024,54(5):867-875.
宋文旭, 冯玉琦, 韩啸枫, 等. 咖啡酸对铜绿假单胞菌群体感应抑制探究[J]. 西北大学学报（自然科学版）, 2024,54(5):867-875. DOI： 10.16152/j.cnki.xdxbzr.2024-05-009.

SONG Wenxu, FENG Yuqi, HAN Xiaofeng, et al. The inhibitory effect of caffeic acid on Pseudomonas aeruginosa QS system and its target[J]. Journal of Northwest University (Natural Science Edition), 2024,54(5):867-875. DOI： 10.16152/j.cnki.xdxbzr.2024-05-009.

摘要

世界范围内，病原菌对抗生素的耐药性日趋严峻，但药物研发效率日趋缓慢，迫切需要新的抗感染药物或药物作用靶点。铜绿假单胞菌群体感应系统（quorum sensing

QS）与其致病性密切相关，寻找靶向QS系统的抑制剂是新型抗感染药物新策略。前期研究发现，以咖啡酸为主要成分的大血藤提取物对铜绿假单胞菌的群体感

应具有转录抑制作用。进一步探究了咖啡酸对铜绿假单胞菌的QS系统相关基因的表达和毒性因子产生的抑制作用；通过分子对接结合缺失突变体感染白菜模型检测，探究了咖啡酸的作用靶点。结果表明：咖啡酸显著抑制铜绿假单胞菌QS系统相关基因

rhlR

、

rhlI

、

pqsA

、

pqsR

及其调控的毒性因子的编码基因如

phzA

1、

lasB

等，进一步抑制该类毒性因子的产生和降低了细菌的运动性和生物被膜，最终降低了铜绿假单胞菌的感染性，其可能通过靶向

pqs

系统发挥其QS抑制作用。

Abstract

Antimicrobial resistance (AMR) of bacteria has increased worldwide dramatically and the development of new antibiotics has been slowed down. Therefore

it is urgent to explore new anti-infective drugs or therapeutics. Quorum sensing (QS) system of pathogen is closely related to its pathogenicity. QS system inhibitors could significantly reduce the pathogenicity of pathogen. QS system is mainly composed of

las

rhl

and

pqs

systems and

Sargentodoxae Caulis

extracts mainly containing caffeic acid which has shown QSI activity. In this study

we proved the antivirulence and antipathogenicity of caffeic acid against

Pseudomonas aeruginosa

at the transcript and product level

then we further investigate the target of caffeic acid in QS system by using molecular docking combining the mutant strains determination. The results indicated that caffeic acid could reduce the expression of QS-related genes

rhlR

rhlI

pqsA

pqsR

as well as virulence related genes such as

phzA

1、

lasB

. Motility ability and biofilm were also suppressed obviously by caffeic acid. Chinese cabbage and fruit fly infection model analysis verified the antipathogenicity of caffeic acid. Caffeic acid might inhibit QS system by targeting the

pqs

system based on the docking analysis and gene mutant strains evaluation on caffeic acid.

关键词

咖啡酸铜绿假单胞菌群体感应系统毒力因子靶点pqs

Keywords

caffeic acidPseudomonas aeruginosaquorum sensing systemvirulence factors target sitepqs

references

SCHABER J A, TRIFFO W J, SUH S J, et al. Pseudomonas aeruginosa forms biofilms in acute infection independent of cell-to-cell signaling [J]. Infect Immun, 2007, 75(8): 3715-3721.

MITTAL R, AGGARWAL S, SHARMA S, et al. Urinary tract infections caused by Pseudomonas aeruginosa: A minireview [J]. J Infect Public Health, 2009, 2(3): 101-111.

ANTIMICROBIAL RESISTANCE COLLABORATORS. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis [J]. Lancet, 2022, 399(10325): 629-655.

丁烨, 戴璐, 俞娟. 抗铜绿假单胞菌感染治疗方法研究进展 [J]. 中华医院感染学杂志, 2020, 30(6): 955-960.

DING Y, DAI L, YU J. Progress of reaserch on treatment of Pseudomonas aeruginosa infection [J] Chinese Journal of Nosocomiology, 2020, 30(6): 955-960.

SOUKARICH F, WILLIAMS P, STOCKS M J, et al. Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: Current position and future perspectives [J]. J Med Chem, 2018, 61(23): 10385-10402.

LEE J, ZHANG L. The hierarchy quorum sensing network in Pseudomonas aeruginosa[J]. Protein & Cell, 2015, 6(1): 26-41.

饶媚, 张素平, 史道华. 铜绿假单胞菌群体感应系统抗菌增效机制研究进展 [J]. 中国感染与化疗杂志, 2019, 19(5): 578-583.

RAO M, ZHANG S P, SHI D H. Study advances of synergistic mecanisms targeting quorum sensing system in Pseudomonas aeruginosa[J] Chinese Journal of Infection and Chemotherapy, 2019, 19(5): 578-583.

PATTNAIK S, AHMED T, RANGANATHAN S K, et al. Aspergillus ochraceopetaliformis SSP13 modulates quorum sensing regulated virulence and biofilm formation in Pseudomonas aeruginosa PAO1 [J]. Biofouling, 2018, 34(4): 410-425.

WARRIER A, SATYAMOORTHY K, MURALI T S. Quorum-sensing regulation of virulence factors in bacterial biofilm [J]. Future Microbiol, 2021, 16: 1003-1021.

何媛, 宋贵波. 铜绿假单胞菌毒力因子及调控机制的研究进展 [J]. 微生物学免疫学进展, 2023, 51(2): 94-99.

HE Y, SONG G B. Research progress on virulence factors and regulatory mechanisms of Pseudomonas aeruginosa[J]. Progress in Microbiology and Immunology, 2023, 51(2): 94-99.

JURADO-MARTÍN I, SAÍNZ-MEJÍAS M, MCCLEAN S. Pseudomonas aeruginosa: An audacious pathogen with an adaptable arsenal of virulence factors[J]. Int J Mol Sci, 2021, 22(6): 3128.

曾莉莉, 史道华, 牛培广. 铜绿假单胞菌群体感应系统及其抑制剂的研究进展 [J]. 中国抗生素杂志, 2014, 39(9): 701-705.

ZENG L L, SHI D H, NIU P G. Research progress in quorum sensing system and its inhibitors of Pseudomonas aeruginosa[J]. Chinese Journal of Antibiotics, 2014, 39(9): 701-705.

KHAN F, BAMUNUARACHCHI N I, TABASSUM N, et al. Caffeic acid and its derivatives: Antimicrobial drugs toward microbial pathogens[J]. J Agric Food Chem, 2021, 69(10): 2979-3004.

WANG G F, SHI L P, REN Y D, et al. Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro [J]. Antiviral Res, 2009, 83(2): 186-190.

任晓娜, 刘宇良, 于航, 等. 缬草、龙脑精油的抑菌活性 [J]. 热带农业科学, 2018, 38(10): 74-78.

REN X N, LIU Y L, YU H, et al. Antibacterial activity of valerian and borneol essenti [J]. Chinese Journal of Tropical Agriculture, 2018, 38(10): 74-78.

BECHER A, SCHWEIZER H P. Integration-proficient Pseudomonas aeruginosa vectors for isolation of single-copy chromosomal lacZ and lux gene fusions[J]. Biotechniques, 2000, 29(5): 948-950.

PEETERS E, NELIS H J, COENYE T. Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates [J]. J Microbiol Methods, 2008, 72(2): 157-165.

ESSAR D W, EBERLY L, HADERO A, et al. Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: Interchangeability of the two anthranilate synthases and evolutionary implications[J]. J Bacteriol, 1990, 172(2): 884-900.

DAI L, WU T Q, XIONG Y S, et al. Ibuprofen-mediated potential inhibition of biofilm development and quorum sensing in Pseudomonas aeruginosa[J]. Life Sci, 2019, 237: 116947.

RASHID M H, KORNBERG A. Inorganic polyphosphate is needed for swimming, swarming, and twitching motilities of Pseudomonas aeruginosa[J]. Proc Natl Acad Sci U S A, 2000, 97(9): 4885-4890.

STARKEY M, RAHME L G. Modeling Pseudomonas aeruginosa pathogenesis in plant hosts [J]. Nat Protoc, 2009, 4(2): 117-124.

CHUGANI S A, WHITETEY M, LEE K M, et al. QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa[J]. Proc Natl Acad Sci U S A, 2001, 98(5): 2752-2757.

CHADHA J, HARJAI K, CHHIBBER S. Repurposing phytochemicals as anti-virulent agents to attenuate quorum sensing-regulated virulence factors and biofilm formation in Pseudomonas aeruginosa[J]. Microb Biotechnol, 2022, 15(6): 1695-1718.

DOLAN S K. Current knowledge and future directions in developing strategies to combat Pseudomonas aeruginosa infection[J]. J Mol Biol, 2020, 432(20): 5509-5528.

AZAM M W, KHAN A U. Updates on the pathogenicity status of Pseudomonas aeruginosa [J]. Drug Discov Today, 2019, 24(1): 350-359.

周志莲, 周彤, 周秀娟, 等. 铜绿假单胞菌群体感应系统及其抑制剂的研究进展 [J]. 中国抗生素杂志, 2023, 48(8): 862-868.

ZHOU Z L, ZHOU T, ZHOU X J, et al. Study on quorum sensing system and its inhibitors of Pseudomonas aeruginosa[J]. Chinese Journal of Antibiotics, 2023, 48(8): 862-868.

O’LOUGHLIN C T, MILLER L C, SIRYAPORN A, et al. A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation [J]. Proc Natl Acad Sci U S A, 2013, 110(44): 17981-17986.

XU W, ZHANG X, WANG L, et al. Effect of chlorogenic acid on the quorum-sensing system of clinically isolated multidrug-resistant Pseudomonas aeruginosa[J]. J Appl Microbiol, 2022, 132(2): 1008-1017.

OUYANG J, FENG W, LAI X, et al. Quercetin inhibits Pseudomonas aeruginosa biofilm formation via the vfr-mediated lasIR system [J]. Microb Pathog, 2020, 149: 104291.

陈沐雨, 潘云萍, 祝司霞. 中草药对铜绿假单胞菌群体感应系统抑制作用的研究进展 [J]. 国外医药(抗生素分册), 2023, 44(4): 217-223.

CHEN M Y, PAN Y P, ZHU S X. Research progress on inhibition of chinese herbal medicine on quorum sensing system of Pseudomonas aeruginosa[J]. World Notes on Antibiotics, 2023, 44(4): 217-223.

汤建, 曹裕旻, 左亚锋, 等. 红藤水溶性部位的LC-MS分析及抗炎活性成分的虚拟筛选 [J]. 中国野生植物资源, 2023, 42(12): 25-29.

TANG J, CAO Y M, ZUO Y F, et al. LC-MS analysis of water-soluble fraction of sargentodoxa cuneata and virtual screening of anti-inflammatory constituents [J]. Chinese Wild Plant Resources, 2023, 42(12): 25-29.

张彦芳, 张娜, 韩正宇, 等. 硫普罗宁联合咖啡酸治疗慢性乙型病毒性肝炎所致白细胞减少的疗效观察 [J]. 现代中西医结合杂志, 2014, 23(18): 1971-1972.

ZHANG Y F, ZHANG N, HAN Z Y, et al. Efficacy observation of sulpiprostone combined with caffeic acid in the treatment of leukopenia caused by chronic hepatitis B [J] Modern Journal of Integrated Traditional Chinese and Western Medicine, 2014, 23(18): 1971-1972.

KALTHOFF S, PAULUSCH S, RUPP A, et al. The coffee ingredients caffeic acid and caffeic acid phenylethyl ester protect against irinotecan-induced leukopenia and oxidative stress response [J]. Br J Pharmacol, 2020, 177(18): 4193-4208.

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