微生物群体感应系统的调控机制及应用研究进展
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摘要
微生物通过群体感应监控范围内菌体数量并调节其自身相关基因的启动表达,进而完成对质粒的接合转移、毒力因子的表达、抗生素的产生和稳定期的进入等一系列相关生命活动的控制,因此群体感应对细菌群体的稳定有重要作用,随着对群体感应系统研究的深入,群体感应相关基因元件及调控原理逐渐清晰,也有许多群体感应系统被应用于实践中。本文中,笔者综述了几种当今研究比较清楚且有代表性的微生物群体感应系统及其调控元件,并且介绍了利用群体感应相关元件构建基因开关实现代谢流的动态调控,以及利用致病菌的群体感应实现微生物的检测及杀灭的应用。
Microorganisms regulate the expression of related genes in cells in the community through quorum sensing,thereby achieving control of a series of related life activities including the production of virulence factors,the biosynthesis of antibiotics,the conjugation of plasmids,and the entry of stable phases.It has important effecton the stability of the bacterial population.With the development of the research on the quorum sensing system,the quorum sensing related gene components and regulatory principles are gradually clarified,and many quorum sensing systems are also applied.This paper reviews several microbial quorum sensing systems and regulatory genes that are well-known and representative in current research,and introduces the use of quorum sensing related components to construct gene switches to achieve dynamic regulation of metabolic fluxes and the use of pathogenic bacteria′s quorum sensing to achieve microbial detection and killing.
Microorganisms regulate the expression of related genes in cells in the community through quorum sensing,thereby achieving control of a series of related life activities including the production of virulence factors,the biosynthesis of antibiotics,the conjugation of plasmids,and the entry of stable phases.It has important effecton the stability of the bacterial population.With the development of the research on the quorum sensing system,the quorum sensing related gene components and regulatory principles are gradually clarified,and many quorum sensing systems are also applied.This paper reviews several microbial quorum sensing systems and regulatory genes that are well-known and representative in current research,and introduces the use of quorum sensing related components to construct gene switches to achieve dynamic regulation of metabolic fluxes and the use of pathogenic bacteria′s quorum sensing to achieve microbial detection and killing.
引文
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[49] BAI A J,VITTAL R R.Quorum sensing inhibitory and antibiofilm activity of essential oils and their in vivo efficacy in food systems[J].Food Biotechnol,2014,28(3):269-292.
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[52] VATTEM D A,MIHALIK K,CRIXELL S H,et al.Dietary phytochemicals as quorum sensing inhibitors[J].Fitoterapia,2007,78(4):302-310.
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[2] MELISSA B M,BASSLER B L.Quorum sensing in bacteria[J].Annu Rev Microbiol,2001,55(1):165-199.
[3] COSGRIFF C J,WHITE C R,TEOH W P,etal.Control of staphylococcus aureus quorum sensing by a membrane embedded peptidase[J].Infect Immun,2019,10(11):11-19.
[4] KAI P,BASSLER B L.Quorum sensing signal response systems in gram negative bacteria[J].Nat Rev Microbiol,2016,14(9):576-588.
[5] MONNET V,GARGANR.Quorumsensing regulators in grampositive bacteria:cherchez le peptide[J].Mol Microbiol,2015,97(2):181-184.
[6] THOMPSON J A,OLIVERIRA R A,DJUKOVIC A,et al.Manipulation of the quorum sensing signal AI-2 affects the antibiotic treated gut microbiota[J].Cell Rep,2015,10(11):1861-1871.
[7] MIYASHIROT,OEHLERT D,RAY V A,et al.The putative oligosaccharide translocase SypK connects biofilm formation with quorum signaling in Vibrio fischeri[J].Microbiol Open,2014,3(6):836-848.
[8] ENGEBRECHT J,NEALSON K,SILVERMAN M.Bacterial bioluminescence:isolation and genetic analysis of functions from Vibrio fischeri[J].Cell,1983,32(3):773-781.
[9] JUNL L,ATTILA C,WANG L,et al.Quorum sensing in Escherichia coli is signaled by AI-2/LsrR:effects on small RNA and biofilm architecture[J].J Bacteriol,2007,189(16):6011-6020.
[10] WILLIAMS P,CAMARA M.Quorum sensing and environmental adaptation in Pseudomonas aeruginosa:a tale of regulatory networks and multifunctional signal molecules[J].Curr Opin Microbiol,2009,12(2):182-191.
[11] LEE J,ZHANG L.The hierarchy quorum sensing network in Pseudomonas aeruginosa[J].Protein Cell,2015,6(1):26-41.
[12] PEARSON J P,DELDEN C V,IGLEWSKI B H.Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals[J].J Bacteriol,1999,181(4):1203-1213.
[13] EVANS K,PASSADOR L,SRIKUMARR,et al.Influence of the MexAB-OprM multidrug efflux system on quorum sensing in Pseudomonas aeruginosa[J].J Bacteriol,1998,180(20):5443-5447.
[14] PASSADOR L,COOK J M,GAMBELLO M J,et al.Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication[J].Science,1993,260:1127-1130.
[15] TODER D S,FERRELL S J,NEZEZON J L,et al.lasA and lasB genes of Pseudomonas aeruginosa:analysis of transcription and gene product activity[J].Infect Immun,1994,62(4):1320-1327.
[16] TODER D S,GAMBELLO M J,IGLEWSKI B H.Pseudomonas aeruginosa LasA:a second elastase under the transcriptional control of lasR[J].Mol Microbiol,2010,5(8):2003-2010.
[17] SEED P C,PASSDOR L,IGLEWSKI B H.Activation of the Pseudomonas aeruginosa lasI gene by LasR and the Pseudomonas autoinducer PAI:an autoinduction regulatory hierarchy[J].J Bacteriol,1995,177(3):654-659.
[18] PEARSON J P,PASSADOR L,IGLEWSKI B H,et al.A second N-acylhomoserine lactone signal produced by Pseudomonas aeruginosa[J].PNAS,1995,92(5):1490-1494.
[19] WINSONM K,CAMARA M,LATIFI A,et al.Multiple N-acyl-L-homoserine lactone signal molecules regulate production of virulence determinants and secondary metabolites in Pseudomonas aeruginosa[J].PNAS,1995,92(20):9427-9431.
[20] TANG H B,DIMANGO E,BRYAN R,et al.Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection[J].Infect Immun,1996,64(1):37-43.
[21] OCHSNER U A,REISERJ.Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa[J].PNAS,1995,92(14):6424-6428.
[22] LATIFI A,WINSON M K,FOGLINO M,et al.Multiple homologues of LuxR and LuxI control expression of virulence determinants and secondary metabolites through quorum sensing in Pseudomonas aeruginosa PAO1[J].Mol Microbiol,2010,17(2):333-343.
[23] LITHGOW J K,DANINO V E,JONE J,et al.Analysis of N-acyl homoserine-lactone quorum-sensing molecules made by different strains and biovars of Rhizobium leguminosarum containing different symbiotic plasmids[J].Plant Soil,2001,232(2):3-12.
[24] LATIFI A,FOGLINO M,TANAKA K,et al.A hierarchical quorum sensing cascade in Pseudomonas aeruginosa links the transcriptional activators LasR and RhIR (VsmR) to expression of the stationaryphase sigma factor RpoS[J].Mol Microbiol,2010,21(6):1137-1146.
[25] GAMBELLO M J,KAYE S,IGLEWSKI B H.LasR of Pseudomonas aeruginosa is a transcriptional activator of the alkaline protease gene (apr) and an enhancer of exotoxin A expression[J].Infect Immun,1993,61(4):1180-1184.
[26] CHAPONHERVE V,AKRIM M,LATIFI A,et al.Regulation of the xcp secretion pathway by multiple quorum-sensing modulons in Pseudomonas aeruginosa[J].Mol Microbiol,2010,24(6):1169-1178.
[27] HASSETTD J,MA J F,ELKINS J G,et al.Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide[J].Mol Microbiol,2010,34(5):1082-1093.
[28] WINZER K,FALCONER C,GARBER N C,et al.The Pseudomonas aeruginosa lectins PA-IL and PA-IIL are controlled by quorum sensing and by RpoS[J].J Bacteriol,2000,182(22):6401-6411.
[29] MCBRAYER D N,CAMERON C D,GANTMAN B K,et al.Rational design of potent activators and inhibitors of the Enterococcus faecalis Fsr quorum sensing circuit[J].ACS Chem Biol,2018,13(9):2673-2681.
[30] WU G,YAN Q,JONES J A,et al.Metabolic burden:cornerstones in synthetic biology and metabolic engineering applications[J].Trends Biotechnol,2016,34(8):652-664.
[31] ANDREAS P,BERND K.Cell density dependent regulation:basic principles and effects on the virulence of gram positive cocci[J].J Infect Dis,2004,8(2):81-95.
[32] LEE T S,KRUPA R A,ZHANGF,et al.BglBrick vectors and datasheets:a synthetic biology platform for gene expression[J].J Biol Eng,2011,5(1):12-26.
[33] BROCKMAN I M,PRATHER K L J.Dynamic metabolic engineering:new strategies for developing responsive cell factories[J].Biotechnol J,2015,10(9):1360-1369.
[34] FARMERW,LIAO J.Improvinglycopene production in Escherichia coli by engineering metabolic control[J].Nat Biotechnol,2000,18(5):533-537.
[35] DAHL R H,ZHANG F,Alonsogutierrez J,et al.Engineering dynamic pathway regulation using stress response promoters[J].Nat Biotechnol,2013,31(11):1039-1046.
[36] SOMA Y,HANAI T.Selfinduced metabolic state switching by a tunable cell density sensor for microbial isopropanol production[J].Metab Eng,2015,30:7-15.
[37] PENG X,WENYAW,LINGYU L,et al.Design and kinetic analysis of a hybrid promoter regulator system for malonyl coA sensing in Escherichia coli[J].ACS Chem Biol,2014,9(2):451-458.
[38] LIU D,XIAO Y,EVANS B S,et al.Negative feedback regulation of fatty acid production based on a malonyl coA sensoractuator[J].ACS Synth Biol,2015,4(2):132-140.
[39] WILLIAMS T C,AVERESCH N J H,WINTER G,et al.Quorum sensing linked RNA interference for dynamic metabolic pathway control in Saccharomyces cerevisiae[J].Metab Eng,2015,29:124-134.
[40] GUPTA A,REIZMAN I M,REISCH C R,et al.Dynamic regulation of metabolic flux in engineered bacteria using a pathway independent quorum sensing circuit[J].Nat Biotechnol,2017,35(3):273-279.
[41] ANAND P,YU T,LINGCHONGY.Optimality and robustness in quorum sensing (QS)mediated regulation of a costly public good enzyme[J].PNAS,2012,109(48):19810-19815.
[42] GRAM L,RAVN L,RASCHM,et al.Food spoilage interactions between food spoilage bacteria[J].J Food Microbiol,2002,78(1):79-97.
[43] MARTINS M L,PINTO C L O,ROCHA R B,etal.Genetic diversity of gram negative,proteolytic,psychrotrophic bacteria isolated from refrigerated raw milk[J].J Food Microbiol,2006,111(2):144-148.
[44] LIU M,GRAY J M,GRIFFITHS M W.Occurrence of proteolytic activity and N-acyl-homoserine lactone signals in the spoilage of aerobically chillstored proteinaceous raw foods[J].J Food Protect,2006,69(11):2729-2737.
[45] BRUHN J B,CHRISTENSEN A B,FLODGAARDLODGAARD L R,et al.Presence of acylated homoserine lactones (AHLs) and AHL producing bacteria in meat and potential role of AHL in spoilage of meat[J].Appl Environ Microb,2004,70(7):4293-4302.
[46] 李学鹏,陈桂芳,仪淑敏,等.食品腐败中细菌群体感应现象的研究进展[J].食品与发酵工业,2015,41(8):244-250.
[47] 郭嘉亮,陈卫民.细菌群体感应信号分子与抑制剂研究进展[J].生命科学,2007,19(2):224-232.
[48] SHOBHARANI P,AGRAWAL R.Interception of quorum sensing signal molecule by furanone to enhance shelf life of fermented milk[J].Food Control,2010,21(1):61-69.
[49] BAI A J,VITTAL R R.Quorum sensing inhibitory and antibiofilm activity of essential oils and their in vivo efficacy in food systems[J].Food Biotechnol,2014,28(3):269-292.
[50] CHAN K G,ATKINSON S,MATHEE K,et al.Characterization of N-acyl-homoserine lactone degrading bacteria associated with the zingiber officinale (ginger) rhizosphere:coexistence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia[J].BMC Microbiol,2011,11(1):51-64.
[51] TRUCHADO P,LOPEZ G F,GIL M I,et al.Quorum sensing inhibitory and antimicrobial activities of honeys and the relationship with individual phenolics[J].Food Chem,2009,115(4):1337-1344.
[52] VATTEM D A,MIHALIK K,CRIXELL S H,et al.Dietary phytochemicals as quorum sensing inhibitors[J].Fitoterapia,2007,78(4):302-310.
[53] BLAIR J M A,WEBBERM A,BAYLAY A J,et al.Molecular mechanisms of antibiotic resistance[J].Nat Rev Microbiol,2015,13(1):42-51.
[54] HRAIECH S,BREGEON F,ROLAIN J M.Bacteriophage based therapy in cystic fibrosis associated Pseudomonas aeruginosa infections:rationale and current status[J].Drug Des Dev Ther,2015,9:3653-3663.
[55] PEWZNERJ Y,TAVAKOLI T S,GRASSME H,et al.Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa[J].EMBO Mol Med,2014,6(9):1205-1214.
[56] ATTI M C D,BERNASCHI P,CARLETTI M,et al.An outbreak of extremely drugresistant Pseudomonas aeruginosa in a tertiary care pediatric hospital in Italy[J].BMC Infect Dis,2014,14(1):494.
[57] SCHLECHT L M,PETERS B M,KROM B P,et al.Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue[J].Microbiology,2015,161(1):168-181.
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