铜绿假单胞菌中Ⅲ型分泌系统调控机制及针对性治疗的研究进展
|
摘要
铜绿假单胞菌是临床上重要的条件致病菌,具有多种毒力因子且极易产生耐药性。Ⅲ型分泌系统(Type Ⅲ secretion system,T3SS)是铜绿假单胞菌中重要的毒性因子分泌系统,该菌通过Ⅲ型分泌系统将多种毒力因子注入到真核宿主细胞内并逃逸宿主细胞免疫系统的清除,引起宿主细胞相应的病理变化。对Ⅲ型分泌系统的研究,不仅有助于明确铜绿假单胞菌的致病机理,更可为临床治疗和药物研发提供理论基础。本文主要对铜绿假单胞菌中Ⅲ型分泌系统的结构、功能、调控机制以及针对性治疗策略等方面的研究进行了综述。
Pseudomonas aeruginosa is a major opportunistic pathogen in clinic and can produce a varietyof virulence factors and high antibiotic resistance. Type Ⅲ secretion system(T3 SS) is an importantvirulence factor secretion system that facilitates the delivery of bacterial effector proteins into eukaryotichost cells. Successful evasion of phagocytosis and subversion of normal host cell physiology to promotepathogenesis depend primarily on the presence of T3 SS. Research on T3 SS will help us understand thepathogenesis of P. aeruginosa and provide a theoretical basis for clinical treatment and the development ofnovel antipathogenic drugs. In this review, the structure, function, regulation mechanism and targetedtreatment of T3 SS in P. aeruginosa are discussed.
Pseudomonas aeruginosa is a major opportunistic pathogen in clinic and can produce a varietyof virulence factors and high antibiotic resistance. Type Ⅲ secretion system(T3 SS) is an importantvirulence factor secretion system that facilitates the delivery of bacterial effector proteins into eukaryotichost cells. Successful evasion of phagocytosis and subversion of normal host cell physiology to promotepathogenesis depend primarily on the presence of T3 SS. Research on T3 SS will help us understand thepathogenesis of P. aeruginosa and provide a theoretical basis for clinical treatment and the development ofnovel antipathogenic drugs. In this review, the structure, function, regulation mechanism and targetedtreatment of T3 SS in P. aeruginosa are discussed.
引文
[1]Lyczak JB,Cannon CL,Pier GB.Lung infections associated with cystic fibrosis[J].Clinical Microbiology Reviews,2002,15(2):194-222
[2]Trautmann M,Lepper PM,Haller M.Ecology of Pseudomonas aeruginosa in the intensive care unit and the evolving role of water outlets as a reservoir of the organism[J].American Journal of Infection Control,2005,33(5S):S41-S49
[3]Hauser AR.The type III secretion system of Pseudomonas aeruginosa:infection by injection[J].Nature Reviews Microbiology,2009,7(9):654-665
[4]Yahr TL,Wolfgang MC.Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system[J].Molecular Microbiology,2006,62(3):631-640
[5]Galle M,Carpentier I,Beyaert R.Structure and function of the type III secretion system of Pseudomonas aeruginosa[J].Current Protein&Peptide Science,2012,13(8):831-842
[6]Cornelis GR.The type III secretion injectisome[J].Nature Reviews Microbiology,2006,4(11):811-825
[7]Pastor A,Chabert J,Louwagie M,et al.PscF is a major component of the Pseudomonas aeruginosa type III secretion needle[J].FEMS Microbiology Letters,2005,253(1):95-101
[8]Mueller CA,Broz P,Cornelis GR.The type III secretion system tip complex and translocon[J].Molecular Microbiology,2008,68(5):1085-1095
[9]Schoehn G,Di Guilmi AM,Lemaire D,et al.Oligomerization of type III secretion proteins PopB and PopD precedes pore formation in Pseudomonas[J].The EMBO Journal,2003,22(19):4957-4967
[10]Goure J,Pastor A,Faudry E,et al.The V antigen of Pseudomonas aeruginosa is required for assembly of the functional PopB/PopD translocation pore in host cell membranes[J].Infection and Immunity,2004,72(8):4741-4750
[11]Faudry E,Vernier G,Neumann E,et al.Synergistic pore formation by type III toxin translocators of Pseudomonas aeruginosa[J].Biochemistry,2006,45(26):8117-8123
[12]Sundin C,Thelaus J,Br?ms JE,et al.Polarisation of type IIItranslocation by Pseudomonas aeruginosa requires PcrG,PcrVand PopN[J].Microbial Pathogenesis,2004,37(6):313-322
[13]Feltman H,Schulert G,Khan S,et al.Prevalence of type IIIsecretion genes in clinical and environmental isolates of Pseudomonas aeruginosa[J].Microbiology,2001,147(10):2659-2669
[14]Burstein D,Satanower S,Simovitch M,et al.Novel type IIIeffectors in Pseudomonas aeruginosa[J].m Bio,2015,6(2):e00161-15
[15]Rocha CL,Coburn J,Rucks EA,et al.Characterization of Pseudomonas aeruginosa exoenzyme S as a bifunctional enzyme in J774A.1 macrophages[J].Infection and Immunity,2003,71(9):5296-5305
[16]Pederson KJ,Vallis AJ,Aktories K,et al.The amino-terminal domain of Pseudomonas aeruginosa ExoS disrupts actin filaments via small-molecular-weight GTP-binding proteins[J].Molecular Microbiology,1999,32(2):393-401
[17]Würtele M,Wolf E,Pederson KJ,et al.How the Pseudomonas aeruginosa ExoS toxin downregulates Rac[J].Nature Structural Biology,2001,8(1):23-26
[18]Ganesan AK,Frank DW,Misra RP,et al.Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple sites[J].Journal of Biological Chemistry,1998,273(13):7332-7337
[19]Kaufman MR,Jia JH,Zeng L,et al.Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS[J].Microbiology,2000,146(10):2531-2541
[20]Barbieri JT,Sun J.Pseudomonas aeruginosa ExoS and ExoT[A]//Amara SG,Bamberg E,Gudermann T,et al.Reviews of Physiology,Biochemistry and Pharmacology[M].Berlin,Heidelberg:Springer,2005:79-92
[21]Kazmierczak BI,Engel JN.Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA,Rac1,and Cdc42[J].Infection and Immunity,2002,70(4):2198-2205
[22]Krall R,Schmidt G,Aktories K,et al.Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein[J].Infection and Immunity,2000,68(10):6066-6068
[23]Deng Q,Sun JJ,Barbieri JT.Uncoupling Crk signal transduction by Pseudomonas exoenzyme T[J].Journal of Biological Chemistry,2005,280(43):35953-35960
[24]Sun JJ,Barbieri JT.Pseudomonas aeruginosa ExoTADP-ribosylates CT10 regulator of kinase(Crk)proteins[J].Journal of Biological Chemistry,2003,278(35):32794-32800
[25]Shafikhani SH,Morales C,Engel J.The Pseudomonas aeruginosa type III secreted toxin ExoT is necessary and sufficient to induce apoptosis in epithelial cells[J].Cellular Microbiology,2008,10(4):994-1007
[26]Yahr TL,Vallis AJ,Hancock MK,et al.ExoY,an adenylate cyclase secreted by the Pseudomonas aeruginosa type IIIsystem[J].Proceedings of the National Academy of Sciences of the United States of America,1998,95(23):13899-13904
[27]Cowell BA,Evans DJ,Fleiszig SMJ.Actin cytoskeleton disruption by ExoY and its effects on Pseudomonas aeruginosa invasion[J].FEMS Microbiology Letters,2005,250(1):71-76
[28]Sayner SL,Frank DW,King J,et al.Paradoxical cAMP-induced lung endothelial hyperpermeability revealed by Pseudomonas aeruginosa ExoY[J].Circulation Research,2004,95(2):196-203
[29]Sato H,Feix JB,Hillard CJ,et al.Characterization of phospholipase activity of the Pseudomonas aeruginosa type IIIcytotoxin,ExoU[J].Journal of Bacteriology,2005,187(3):1192-1195
[30]Rabin SDP,Hauser AR.Functional regions of the Pseudomonas aeruginosa cytotoxin ExoU[J].Infection and Immunity,2005,73(1):573-582
[31]Sato H,Frank DW,Hillard CJ,et al.The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin,ExoU[J].The EMBO Journal,2003,22(12):2959-2969
[32]Schulert GS,Feltman H,Rabin SDP,et al.Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas aeruginosa isolates obtained from patients with hospital-acquired pneumonia[J].The Journal of Infectious Diseases,2003,188(11):1695-1706
[33]Parsot C,Hamiaux C,Page AL.The various and varying roles of specific chaperones in type III secretion systems[J].Current Opinion in Microbiology,2003,6(1):7-14
[34]Shen DK,Quenee L,Bonnet M,et al.Orf1/SpcS Chaperones ExoS for Type Three Secretion by Pseudomonas aeruginosa[J].Biomedical and Environmental Sciences,2008,21(2):103-109
[35]Finck-Barbancon V,Yahr TL,Frank DW.Identification and characterization of SpcU,a chaperone required for efficient secretion of the ExoU cytotoxin[J].Journal of Bacteriology,1998,180(23):6224-6231
[36]Diaz MR,King JM,Yahr TL.Intrinsic and extrinsic regulation of type III secretion gene expression in Pseudomonas aeruginosa[J].Frontiers in Microbiology,2011,2:89
[37]Luo Q,Jin SG.Molecular determinants in regulating Pseudomonas aeruginosa type III secretion system-a review[J].Acta Microbiologica Sinica,2008,48(10):1413-1417(in Chinese)罗勤,金守光.铜绿假单胞菌III型分泌系统的分子调控机制[J].微生物学报,2008,48(10):1413-1417
[38]Frank DW.The exoenzyme S regulon of Pseudomonas aeruginosa[J].Molecular Microbiology,1997,26(4):621-629
[39]Hovey AK,Frank DW.Analyses of the DNA-binding and transcriptional activation properties of ExsA,the transcriptional activator of the Pseudomonas aeruginosa exoenzyme Sregulon[J].Journal of Bacteriology,1995,177(15):4427-4436
[40]Dasgupta N,Lykken GL,Wolfgang MC,et al.A novel anti-anti-activator mechanism regulates expression of the Pseudomonas aeruginosa type III secretion system[J].Molecular Microbiology,2004,53(1):297-308
[41]McCaw ML,Lykken GL,Singh PK,et al.ExsD is a negative regulator of the Pseudomonas aeruginosa type III secretion regulon[J].Molecular Microbiology,2002,46(4):1123-1133
[42]Urbanowski ML,Brutinel ED,Yahr TL.Translocation of ExsEinto Chinese hamster ovary cells is required for transcriptional induction of the Pseudomonas aeruginosa type III secretion system[J].Infection and Immunity,2007,75(9):4432-4439
[43]Albus AM,Pesci EC,Runyen-Janecky LJ,et al.Vfr controls quorum sensing in Pseudomonas aeruginosa[J].Journal of Bacteriology,1997,179(12):3928-3935
[44]Beatson SA,Whitchurch CB,Sargent JL,et al.Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa[J].Journal of Bacteriology,2002,184(13):3605-3613
[45]West SE,Sample AK,Runyen-Janecky LJ.The vfr gene product,required for Pseudomonas aeruginosa exotoxin A and protease production,belongs to the cyclic AMP receptor protein family[J].Journal of Bacteriology,1994,176(24):7532-7542
[46]Wolfgang MC,Lee VT,Gilmore ME,et al.Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway[J].Developmental Cell,2003,4(2):253-263
[47]Rietsch A,Mekalanos JJ.Metabolic regulation of type IIIsecretion gene expression in Pseudomonas aeruginosa[J].Molecular Microbiology,2006,59(3):807-820
[48]Marsden AE,Intile PJ,Schulmeyer KH,et al.Vfr directly activates exsA transcription to regulate expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2016,198(9):1442-1450
[49]Brencic A,McFarland KA,McManus HR,et al.The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs[J].Molecular Microbiology,2009,73(3):434-445
[50]Allsopp LP,Wood TE,Howard SA,et al.RsmA and AmrZorchestrate the assembly of all three type VI secretion systems in Pseudomonas aeruginosa[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(29):7707-7712
[51]Brencic A,Lory S.Determination of the regulon and identification of novel m RNA targets of Pseudomonas aeruginosa RsmA[J].Molecular Microbiology,2009,72(3):612-632
[52]Irie Y,Starkey M,Edwards AN,et al.Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA[J].Molecular Microbiology,2010,78(1):158-172
[53]Broder UN,Jaeger T,Jenal U.LadS is a calcium-responsive kinase that induces acute-to-chronic virulence switch in Pseudomonas aeruginosa[J].Nature Microbiology,2016,2:16184
[54]Chambonnier G,Roux L,Redelberger D,et al.The hybrid histidine kinase LadS forms a multicomponent signal transduction system with the GacS/GacA two-component system in Pseudomonas aeruginosa[J].PLoS Genetics,2016,12(5):e1006032
[55]Ventre I,Goodman AL,Vallet-Gely I,et al.Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(1):171-176
[56]Goodman AL,Kulasekara B,Rietsch A,et al.A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa[J].Developmental Cell,2004,7(5):745-754
[57]Goodman AL,Merighi M,Hyodo M,et al.Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen[J].Genes&Development,2009,23(2):249-259
[58]Kong WN,Chen L,Zhao JQ,et al.Hybrid sensor kinase PA1611 in Pseudomonas aeruginosa regulates transitions between acute and chronic infection through direct interaction with RetS[J].Molecular Microbiology,2013,88(4):784-797
[59]Bhagirath AY,Pydi SP,Li YQ,et al.Characterization of the direct interaction between hybrid sensor kinases PA1611 and RetS that controls biofilm formation and the type III secretion system in Pseudomonas aeruginosa[J].ACS Infectious Diseases,2017,3(2):162-175
[60]Zhu M,Zhao JR,Kang HP,et al.Modulation of type IIIsecretion system in Pseudomonas aeruginosa:involvement of the PA4857 gene product[J].Frontiers in Microbiology,2016,7:7
[61]R?mling U,Galperin MY,Gomelsky M.Cyclic di-GMP:the first 25 years of a universal bacterial second messenger[J].Microbiology and Molecular Biology Reviews,2013,77(1):1-52
[62]Moscoso JA,Mikkelsen H,Heeb S,et al.The Pseudomonas aeruginosa sensor RetS switches type III and type VI secretion via c-di-GMP signalling[J].Environmental Microbiology,2011,13(12):3128-3138
[63]Moscoso JA,Jaeger T,Valentini M,et al.The diguanylate cyclase SadC is a central player in Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa[J].Journal of Bacteriology,2014,196(23):4081-4088
[64]Li KW,Xu C,Jin YX,et al.SuhB is a regulator of multiple virulence genes and essential for pathogenesis of Pseudomonas aeruginosa[J].mBio,2013,4(6):e00419-13
[65]Li KW,Yang GJ,Debru AB,et al.SuhB regulates the motile-sessile switch in Pseudomonas aeruginosa through the Gac/Rsm pathway and c-di-GMP signaling[J].Frontiers in Microbiology,2017,8:1045
[66]Bhagirath AY,Somayajula D,Li YQ,et al.CmpX affects virulence in Pseudomonas aeruginosa through the Gac/Rsm signaling pathway and by modulating c-di-GMP levels[J].The Journal of Membrane Biology,2018,251(1):35-49
[67]Aragon IM,Pérez-Mendoza D,Moscoso JA,et al.Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp.infections[J].Environmental Microbiology,2015,17(11):4332-4351
[68]Rossello J,Lima A,Gil M,et al.The EAL-domain protein FcsRregulates flagella,chemotaxis and type III secretion system in Pseudomonas aeruginosa by a phosphodiesterase independent mechanism[J].Scientific Reports,2017,7(1):10281
[69]Chen GK,Zhao Q,Zhu F,et al.Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa[J].Microbiological Research,2016,188-189:90-96
[70]Abisado RG,Benomar S,Klaus JR,et al.Bacterial quorum sensing and microbial community interactions[J].mBio,2018,9(3):e02331-17
[71]Lee J,Zhang LH.The hierarchy quorum sensing network in Pseudomonas aeruginosa[J].Protein&Cell,2015,6(1):26-41
[72]Bleves S,Soscia C,Nogueira-Orlandi P,et al.Quorum sensing negatively controls type III secretion regulon expression in Pseudomonas aeruginosa PAO1[J].Journal of Bacteriology,2005,187(11):3898-3902
[73]Hogardt M,Roeder M,Schreff AM,et al.Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS[J].Microbiology,2004,150(4):843-851
[74]Kong WN,Liang HH,Shen LX,et al.Regulation of type IIIsecretion system by Rhl and PQS quorum sensing systems in Pseudomonas aeruginosa[J].Acta Microbiologica Sinica,2009,49(9):1158-1164(in Chinese)孔伟娜,梁海华,沈立新,等.铜绿假单胞菌中III型分泌系统受Rhl和PQS群体感应系统调节[J].微生物学报,2009,49(9):1158-1164
[75]Singh G,Wu B,Baek MS,et al.Secretion of Pseudomonas aeruginosa type III cytotoxins is dependent on pseudomonas quinolone signal concentration[J].Microbial Pathogenesis,2010,49(4):196-203
[76]Liang HH,Deng X,Li XF,et al.Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa[J].Nucleic Acids Research,2014,42(16):10307-10320
[77]Liang HH,Kong WN,Shen T,et al.The effect of pmpR on the type III secretion system in Pseudomonas aeruginosa[J].Chinese Science Bulletin,2012,57(19):2413-2418
[78]Allmond LR,Ajayi T,Moriyama K,et al.V-antigen genotype and phenotype analyses of clinical isolates of Pseudomonas aeruginosa[J].Journal of Clinical Microbiology,2004,42(8):3857-3860
[79]Martin DW,Schurr MJ,Mudd MH,et al.Mechanism of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients[J].Proceedings of the National Academy of Sciences of the United States of America,1993,90(18):8377-8381
[80]Wu WH,Badrane H,Arora S,et al.MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa[J].Journal of Bacteriology,2004,186(22):7575-7585
[81]Schurr MJ,Yu H,Martinez-Salazar JM,et al.Control of AlgU,a member of the sigma E-like family of stress sigma factors,by the negative regulators MucA and MucB and Pseudomonas aeruginosa conversion to mucoidy in cystic fibrosis[J].Journal of Bacteriology,1996,178(16):4997-5004
[82]Wozniak DJ,Ohman DE.Transcriptional analysis of the Pseudomonas aeruginosa genes algR,algB,and algD reveals a hierarchy of alginate gene expression which is modulated by algT[J].Journal of Bacteriology,1994,176(19):6007-6014
[83]Intile PJ,Diaz MR,Urbanowski ML,et al.The AlgZRtwo-component system recalibrates the RsmAYZposttranscriptional regulatory system to inhibit expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2014,196(2):357-366
[84]Jones AK,Fulcher NB,Balzer GJ,et al.Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling[J].Journal of Bacteriology,2010,192(21):5709-5717
[85]Aspedon A,Palmer K,Whiteley M.Microarray analysis of the osmotic stress response in Pseudomonas aeruginosa[J].Journal of Bacteriology,2006,188(7):2721-2725
[86]Wu WH,Jin SG.PtrB of Pseudomonas aeruginosa suppresses the type III secretion system under the stress of DNAdamage[J].Journal of Bacteriology,2005,187(17):6058-6068
[87]Elsen S,Ragno M,Attree I.PtrA is a periplasmic protein involved in Cu tolerance in Pseudomonas aeruginosa[J].Journal of Bacteriology,2011,193(13):3376-3378
[88]Ha UH,Kim J,Badrane H,et al.An in vivo inducible gene of Pseudomonas aeruginosa encodes an anti-ExsA to suppress the type III secretion system[J].Molecular Microbiology,2004,54(2):307-320
[89]Anderson GG,Yahr TL,Lovewell RR,et al.The Pseudomonas aeruginosa magnesium transporter MgtE inhibits transcription of the type III secretion system[J].Infection and Immunity,2010,78(3):1239-1249
[90]Chakravarty S,Melton CN,Bailin A,et al.Pseudomonas aeruginosa magnesium transporter MgtE inhibits type IIIsecretion system gene expression by stimulating rsmYZtranscription[J].Journal of Bacteriology,2017,199(23):e00268-17
[91]Chung JCS,Rzhepishevska O,Ramstedt M,et al.Type IIIsecretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is stimulated by isocitrate lyase activity[J].Open Biology,2013,3(1):120131
[92]O’Callaghan J,Reen FJ,Adams C,et al.Low oxygen induces the type III secretion system in Pseudomonas aeruginosa via modulation of the small RNAs rsmZ and rsmY[J].Microbiology,2011,157(12):3417-3428
[93]Van Alst NE,Wellington M,Clark VL,et al.Nitrite reductase NirS is required for type III secretion system expression and virulence in the human monocyte cell line THP-1 by Pseudomonas aeruginosa[J].Infection and Immunity,2009,77(10):4446-4454
[94]Barbier M,Damron FH,Bielecki P,et al.From the environment to the host:re-wiring of the transcriptome of Pseudomonas aeruginosa from 22°C to 37°C[J].PLoS One,2014,9(2):e89941
[95]Kang Y,Lunin VV,Skarina T,et al.The long-chain fatty acid sensor,PsrA,modulates the expression of rpoS and the type IIIsecretion exsCEBA operon in Pseudomonas aeruginosa[J].Molecular Microbiology,2009,73(1):120-136
[96]Shen DK,Filopon D,Kuhn L,et al.PsrA is a positive transcriptional regulator of the type III secretion system in Pseudomonas aeruginosa[J].Infection and Immunity,2006,74(2):1121-1129
[97]Dacheux D,Epaulard O,de Groot A,et al.Activation of the Pseudomonas aeruginosa type III secretion system requires an intact pyruvate dehydrogenase aceAB operon[J].Infection and Immunity,2002,70(7):3973-3977
[98]O’Callaghan J,Reen JF,Adams C,et al.A novel host-responsive sensor mediates virulence and type III secretion during Pseudomonas aeruginosa-host cell interactions[J].Microbiology,2012,158(Pt 4):1057-1070
[99]Zhou L,Wang J,Zhang LH.Modulation of bacterial type IIIsecretion system by a spermidine transporter dependent signaling pathway[J].PLoS One,2007,2(12):e1291
[100]Linares JF,López JA,Camafeita E,et al.Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa[J].Journal of Bacteriology,2005,187(4):1384-1391
[101]Rietsch A,Wolfgang MC,Mekalanos JJ.Effect of metabolic imbalance on expression of type III secretion genes in Pseudomonas aeruginosa[J].Infection and Immunity,2004,72(3):1383-1390
[102]Dong YH,Zhang XF,Zhang LH.The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa[J].MicrobiologyOpen,2013,2(1):161-172
[103]Yeung ATY,Bains M,Hancock REW.The sensor kinase CbrAis a global regulator that modulates metabolism,virulence,and antibiotic resistance in Pseudomonas aeruginosa[J].Journal of Bacteriology,2011,193(4):918-931
[104]Shen DK,Filopon D,Chaker H,et al.High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system:implications for tryptophan catabolites[J].Microbiology,2008,154(8):2195-2208
[105]Mou R,Du X,Wang XH,et al.Pseudomonas aeruginosa gene pfm affects the expression levels of type III secretion system effectors[J].Microbiology China,2013,40(8):1462-1467(in Chinese)牟锐,杜星,王雪涵,等.铜绿假单胞菌pfm基因对三型分泌系统效应蛋白的影响[J].微生物学通报,2013,40(8):1462-1467
[106]Neidig A,Yeung ATY,Rosay T,et al.TypA is involved in virulence,antimicrobial resistance and biofilm formation in Pseudomonas aeruginosa[J].BMC Microbiology,2013,13:77
[107]McCarthy RR,Mooij MJ,Reen FJ,et al.A new regulator of pathogenicity(bvlR)is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa[J].Microbiology,2014,160(Pt 7):1488-1500
[108]Intile PJ,Balzer GJ,Wolfgang MC,et al.The RNA helicase DeaD stimulates ExsA translation to promote expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2015,197(16):2664-2674
[109]Wang BB,Li B,Liang Y,et al.Pleiotropic effects of temperature-regulated 2-OH-lauroytransferase(PA0011)on Pseudomonas aeruginosa antibiotic resistance,virulence and type III secretion system[J].Microbial Pathogenesis,2016,91:5-17
[110]Chen RH,Weng YD,Zhu F,et al.Polynucleotide phosphorylase regulates multiple virulence factors and the stabilities of small RNAs RsmY/Z in Pseudomonas aeruginosa[J].Frontiers in Microbiology,2016,7:247
[111]Li M,Long YQ,Liu Y,et al.HigB of Pseudomonas aeruginosa enhances killing of phagocytes by up-regulating the type IIIsecretion system in ciprofloxacin induced persister cells[J].Frontiers in Cellular and Infection Microbiology,2016,6:125
[112]Pérez-Gallego M,Torrens G,Castillo-Vera J,et al.Impact of AmpC derepression on fitness and virulence:the mechanism or the pathway?[J].mBio,2016,7(5):e01783-16
[113]Deng X,Li M,Pan XL,et al.Fis regulates type III secretion system by influencing the transcription of exsA in Pseudomonas aeruginosa strain PA14[J].Frontiers in Microbiology,2017,8:669
[114]Zhang YF,Han K,Chandler CE,et al.Probing the sRNAregulatory landscape of P.aeruginosa:post-transcriptional control of determinants of pathogenicity and antibiotic susceptibility[J].Molecular Microbiology,2017,106(6):919-937
[115]Anantharajah A,Mingeot-Leclercq MP,Bambeke F.Targeting the type three secretion system in Pseudomonas aeruginosa[J].Trends in Pharmacological Sciences,2016,37(9):734-749
[116]Yamazaki A,Li J,Zeng Q,et al.Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system[J].Antimicrobial Agents and Chemotherapy,2012,56(1):36-43
[117]Shan JM,Wu XG,Yuan XC,et al.The influence of cinnamic acid derivatives on the type III secretion system of Pseudomonas aeruginosa PAO1[J].Microbiology China,2014,41(10):2061-2069(in Chinese)单金明,吴小刚,袁小琛,等.肉桂酸衍生物对铜绿假单胞菌PAO1 III型分泌系统的影响[J].微生物学通报,2014,41(10):2061-2069
[118]Grier MC,Garrity-Ryan LK,Bartlett VJ,et al.N-hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa:in vitro anti-virulence activity and metabolic stability[J].Bioorganic&Medicinal Chemistry Letters,2010,20(11):3380-3383
[119]Marsden AE,King JM,Spies MA,et al.Inhibition of Pseudomonas aeruginosa ExsA DNA-binding activity by N-hydroxybenzimidazoles[J].Antimicrobial Agents and Chemotherapy,2016,60(2):766-776
[120]Wang D,Zetterstrom CE,Gabrielsen M,et al.Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds[J].Journal of Biological Chemistry,2011,286(34):29922-29931
[121]Enquist PA,Gylfe?,H?gglund U,et al.Derivatives of8-hydroxyquinoline-antibacterial agents that target intra-and extracellular Gram-negative pathogens[J].Bioorganic&Medicinal Chemistry Letters,2012,22(10):3550-3553
[122]Felise HB,Nguyen HV,Pfuetzner RA,et al.An inhibitor of gram-negative bacterial virulence protein secretion[J].Cell Host&Microbe,2008,4(4):325-336
[123]Aiello D,Williams JD,Majgier-Baranowska H,et al.Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion[J].Antimicrobial Agents and Chemotherapy,2010,54(5):1988-1999
[124]Zhang CF,Wu XG,Li Y,et al.Synthesis and bioactivity of novel inhibitors for type III secretion system of Pseudomonas aeruginosa PAO1[J].Chinese Journal of Organic Chemistry,2013,33(6):1309-1318(in Chinese)张成芳,吴小刚,李燕,等.铜绿假单胞菌PAO1 III型分泌系统新型抑制剂的合成和生物活性研究[J].有机化学,2013,33(6):1309-1318
[125]Gu LL,Wu XG,Yuan XC,et al.Regulation of type III secretion system inhibitors on virulence factors of Pseudomonas aeruginosa PAO1[J].Microbiology China,2014,41(11):2318-2324(in Chinese)顾玲玲,吴小刚,袁小琛,等.III型分泌系统抑制剂对铜绿假单胞菌PAO1毒性因子的影响[J].微生物学通报,2014,41(11):2318-2324
[126]Frank DW,Vallis A,Wiener-Kronish JP,et al.Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV[J].The Journal of Infectious Diseases,2002,186(1):64-73
[127]Imamura Y,Yanagihara K,Fukuda Y,et al.Effect of anti-PcrVantibody in a murine chronic airway Pseudomonas aeruginosa infection model[J].European Respiratory Journal,2007,29(5):965-968
[128]Sawa T,Yahr TL,Ohara M,et al.Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury[J].Nature Medicine,1999,5(4):392-398
[129]Lynch SV,Flanagan JL,Sawa T,et al.Polymorphisms in the Pseudomonas aeruginosa type III secretion protein,PcrV-implications for anti-PcrV immunotherapy[J].Microbial Pathogenesis,2010,48(6):197-204
[130]DiGiandomenico A,Keller AE,Gao CH,et al.Amultifunctional bispecific antibody protects against Pseudomonas aeruginosa[J].Science Translational Medicine,2014,6(262):262ra155
[131]Fran?ois B,Luyt CE,Dugard A,et al.Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized with Pseudomonas aeruginosa:a randomized,double-blind,placebo-controlled trial[J].Critical Care Medicine,2012,40(8):2320-2326
[132]Arnoldo A,Curak J,Kittanakom S,et al.Identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme Susing a yeast phenotypic screen[J].PLoS Genetics,2008,4(2):e1000005
[133]Lee VT,Pukatzki S,Sato H,et al.Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU[J].Infection and Immunity,2007,75(3):1089-1098
[134]Kim D,Baek J,Song J,et al.Identification of arylsulfonamides as ExoU inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2014,24(16):3823-3825
[2]Trautmann M,Lepper PM,Haller M.Ecology of Pseudomonas aeruginosa in the intensive care unit and the evolving role of water outlets as a reservoir of the organism[J].American Journal of Infection Control,2005,33(5S):S41-S49
[3]Hauser AR.The type III secretion system of Pseudomonas aeruginosa:infection by injection[J].Nature Reviews Microbiology,2009,7(9):654-665
[4]Yahr TL,Wolfgang MC.Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system[J].Molecular Microbiology,2006,62(3):631-640
[5]Galle M,Carpentier I,Beyaert R.Structure and function of the type III secretion system of Pseudomonas aeruginosa[J].Current Protein&Peptide Science,2012,13(8):831-842
[6]Cornelis GR.The type III secretion injectisome[J].Nature Reviews Microbiology,2006,4(11):811-825
[7]Pastor A,Chabert J,Louwagie M,et al.PscF is a major component of the Pseudomonas aeruginosa type III secretion needle[J].FEMS Microbiology Letters,2005,253(1):95-101
[8]Mueller CA,Broz P,Cornelis GR.The type III secretion system tip complex and translocon[J].Molecular Microbiology,2008,68(5):1085-1095
[9]Schoehn G,Di Guilmi AM,Lemaire D,et al.Oligomerization of type III secretion proteins PopB and PopD precedes pore formation in Pseudomonas[J].The EMBO Journal,2003,22(19):4957-4967
[10]Goure J,Pastor A,Faudry E,et al.The V antigen of Pseudomonas aeruginosa is required for assembly of the functional PopB/PopD translocation pore in host cell membranes[J].Infection and Immunity,2004,72(8):4741-4750
[11]Faudry E,Vernier G,Neumann E,et al.Synergistic pore formation by type III toxin translocators of Pseudomonas aeruginosa[J].Biochemistry,2006,45(26):8117-8123
[12]Sundin C,Thelaus J,Br?ms JE,et al.Polarisation of type IIItranslocation by Pseudomonas aeruginosa requires PcrG,PcrVand PopN[J].Microbial Pathogenesis,2004,37(6):313-322
[13]Feltman H,Schulert G,Khan S,et al.Prevalence of type IIIsecretion genes in clinical and environmental isolates of Pseudomonas aeruginosa[J].Microbiology,2001,147(10):2659-2669
[14]Burstein D,Satanower S,Simovitch M,et al.Novel type IIIeffectors in Pseudomonas aeruginosa[J].m Bio,2015,6(2):e00161-15
[15]Rocha CL,Coburn J,Rucks EA,et al.Characterization of Pseudomonas aeruginosa exoenzyme S as a bifunctional enzyme in J774A.1 macrophages[J].Infection and Immunity,2003,71(9):5296-5305
[16]Pederson KJ,Vallis AJ,Aktories K,et al.The amino-terminal domain of Pseudomonas aeruginosa ExoS disrupts actin filaments via small-molecular-weight GTP-binding proteins[J].Molecular Microbiology,1999,32(2):393-401
[17]Würtele M,Wolf E,Pederson KJ,et al.How the Pseudomonas aeruginosa ExoS toxin downregulates Rac[J].Nature Structural Biology,2001,8(1):23-26
[18]Ganesan AK,Frank DW,Misra RP,et al.Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple sites[J].Journal of Biological Chemistry,1998,273(13):7332-7337
[19]Kaufman MR,Jia JH,Zeng L,et al.Pseudomonas aeruginosa mediated apoptosis requires the ADP-ribosylating activity of ExoS[J].Microbiology,2000,146(10):2531-2541
[20]Barbieri JT,Sun J.Pseudomonas aeruginosa ExoS and ExoT[A]//Amara SG,Bamberg E,Gudermann T,et al.Reviews of Physiology,Biochemistry and Pharmacology[M].Berlin,Heidelberg:Springer,2005:79-92
[21]Kazmierczak BI,Engel JN.Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein for RhoA,Rac1,and Cdc42[J].Infection and Immunity,2002,70(4):2198-2205
[22]Krall R,Schmidt G,Aktories K,et al.Pseudomonas aeruginosa ExoT is a Rho GTPase-activating protein[J].Infection and Immunity,2000,68(10):6066-6068
[23]Deng Q,Sun JJ,Barbieri JT.Uncoupling Crk signal transduction by Pseudomonas exoenzyme T[J].Journal of Biological Chemistry,2005,280(43):35953-35960
[24]Sun JJ,Barbieri JT.Pseudomonas aeruginosa ExoTADP-ribosylates CT10 regulator of kinase(Crk)proteins[J].Journal of Biological Chemistry,2003,278(35):32794-32800
[25]Shafikhani SH,Morales C,Engel J.The Pseudomonas aeruginosa type III secreted toxin ExoT is necessary and sufficient to induce apoptosis in epithelial cells[J].Cellular Microbiology,2008,10(4):994-1007
[26]Yahr TL,Vallis AJ,Hancock MK,et al.ExoY,an adenylate cyclase secreted by the Pseudomonas aeruginosa type IIIsystem[J].Proceedings of the National Academy of Sciences of the United States of America,1998,95(23):13899-13904
[27]Cowell BA,Evans DJ,Fleiszig SMJ.Actin cytoskeleton disruption by ExoY and its effects on Pseudomonas aeruginosa invasion[J].FEMS Microbiology Letters,2005,250(1):71-76
[28]Sayner SL,Frank DW,King J,et al.Paradoxical cAMP-induced lung endothelial hyperpermeability revealed by Pseudomonas aeruginosa ExoY[J].Circulation Research,2004,95(2):196-203
[29]Sato H,Feix JB,Hillard CJ,et al.Characterization of phospholipase activity of the Pseudomonas aeruginosa type IIIcytotoxin,ExoU[J].Journal of Bacteriology,2005,187(3):1192-1195
[30]Rabin SDP,Hauser AR.Functional regions of the Pseudomonas aeruginosa cytotoxin ExoU[J].Infection and Immunity,2005,73(1):573-582
[31]Sato H,Frank DW,Hillard CJ,et al.The mechanism of action of the Pseudomonas aeruginosa-encoded type III cytotoxin,ExoU[J].The EMBO Journal,2003,22(12):2959-2969
[32]Schulert GS,Feltman H,Rabin SDP,et al.Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas aeruginosa isolates obtained from patients with hospital-acquired pneumonia[J].The Journal of Infectious Diseases,2003,188(11):1695-1706
[33]Parsot C,Hamiaux C,Page AL.The various and varying roles of specific chaperones in type III secretion systems[J].Current Opinion in Microbiology,2003,6(1):7-14
[34]Shen DK,Quenee L,Bonnet M,et al.Orf1/SpcS Chaperones ExoS for Type Three Secretion by Pseudomonas aeruginosa[J].Biomedical and Environmental Sciences,2008,21(2):103-109
[35]Finck-Barbancon V,Yahr TL,Frank DW.Identification and characterization of SpcU,a chaperone required for efficient secretion of the ExoU cytotoxin[J].Journal of Bacteriology,1998,180(23):6224-6231
[36]Diaz MR,King JM,Yahr TL.Intrinsic and extrinsic regulation of type III secretion gene expression in Pseudomonas aeruginosa[J].Frontiers in Microbiology,2011,2:89
[37]Luo Q,Jin SG.Molecular determinants in regulating Pseudomonas aeruginosa type III secretion system-a review[J].Acta Microbiologica Sinica,2008,48(10):1413-1417(in Chinese)罗勤,金守光.铜绿假单胞菌III型分泌系统的分子调控机制[J].微生物学报,2008,48(10):1413-1417
[38]Frank DW.The exoenzyme S regulon of Pseudomonas aeruginosa[J].Molecular Microbiology,1997,26(4):621-629
[39]Hovey AK,Frank DW.Analyses of the DNA-binding and transcriptional activation properties of ExsA,the transcriptional activator of the Pseudomonas aeruginosa exoenzyme Sregulon[J].Journal of Bacteriology,1995,177(15):4427-4436
[40]Dasgupta N,Lykken GL,Wolfgang MC,et al.A novel anti-anti-activator mechanism regulates expression of the Pseudomonas aeruginosa type III secretion system[J].Molecular Microbiology,2004,53(1):297-308
[41]McCaw ML,Lykken GL,Singh PK,et al.ExsD is a negative regulator of the Pseudomonas aeruginosa type III secretion regulon[J].Molecular Microbiology,2002,46(4):1123-1133
[42]Urbanowski ML,Brutinel ED,Yahr TL.Translocation of ExsEinto Chinese hamster ovary cells is required for transcriptional induction of the Pseudomonas aeruginosa type III secretion system[J].Infection and Immunity,2007,75(9):4432-4439
[43]Albus AM,Pesci EC,Runyen-Janecky LJ,et al.Vfr controls quorum sensing in Pseudomonas aeruginosa[J].Journal of Bacteriology,1997,179(12):3928-3935
[44]Beatson SA,Whitchurch CB,Sargent JL,et al.Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa[J].Journal of Bacteriology,2002,184(13):3605-3613
[45]West SE,Sample AK,Runyen-Janecky LJ.The vfr gene product,required for Pseudomonas aeruginosa exotoxin A and protease production,belongs to the cyclic AMP receptor protein family[J].Journal of Bacteriology,1994,176(24):7532-7542
[46]Wolfgang MC,Lee VT,Gilmore ME,et al.Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway[J].Developmental Cell,2003,4(2):253-263
[47]Rietsch A,Mekalanos JJ.Metabolic regulation of type IIIsecretion gene expression in Pseudomonas aeruginosa[J].Molecular Microbiology,2006,59(3):807-820
[48]Marsden AE,Intile PJ,Schulmeyer KH,et al.Vfr directly activates exsA transcription to regulate expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2016,198(9):1442-1450
[49]Brencic A,McFarland KA,McManus HR,et al.The GacS/GacA signal transduction system of Pseudomonas aeruginosa acts exclusively through its control over the transcription of the RsmY and RsmZ regulatory small RNAs[J].Molecular Microbiology,2009,73(3):434-445
[50]Allsopp LP,Wood TE,Howard SA,et al.RsmA and AmrZorchestrate the assembly of all three type VI secretion systems in Pseudomonas aeruginosa[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(29):7707-7712
[51]Brencic A,Lory S.Determination of the regulon and identification of novel m RNA targets of Pseudomonas aeruginosa RsmA[J].Molecular Microbiology,2009,72(3):612-632
[52]Irie Y,Starkey M,Edwards AN,et al.Pseudomonas aeruginosa biofilm matrix polysaccharide Psl is regulated transcriptionally by RpoS and post-transcriptionally by RsmA[J].Molecular Microbiology,2010,78(1):158-172
[53]Broder UN,Jaeger T,Jenal U.LadS is a calcium-responsive kinase that induces acute-to-chronic virulence switch in Pseudomonas aeruginosa[J].Nature Microbiology,2016,2:16184
[54]Chambonnier G,Roux L,Redelberger D,et al.The hybrid histidine kinase LadS forms a multicomponent signal transduction system with the GacS/GacA two-component system in Pseudomonas aeruginosa[J].PLoS Genetics,2016,12(5):e1006032
[55]Ventre I,Goodman AL,Vallet-Gely I,et al.Multiple sensors control reciprocal expression of Pseudomonas aeruginosa regulatory RNA and virulence genes[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(1):171-176
[56]Goodman AL,Kulasekara B,Rietsch A,et al.A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa[J].Developmental Cell,2004,7(5):745-754
[57]Goodman AL,Merighi M,Hyodo M,et al.Direct interaction between sensor kinase proteins mediates acute and chronic disease phenotypes in a bacterial pathogen[J].Genes&Development,2009,23(2):249-259
[58]Kong WN,Chen L,Zhao JQ,et al.Hybrid sensor kinase PA1611 in Pseudomonas aeruginosa regulates transitions between acute and chronic infection through direct interaction with RetS[J].Molecular Microbiology,2013,88(4):784-797
[59]Bhagirath AY,Pydi SP,Li YQ,et al.Characterization of the direct interaction between hybrid sensor kinases PA1611 and RetS that controls biofilm formation and the type III secretion system in Pseudomonas aeruginosa[J].ACS Infectious Diseases,2017,3(2):162-175
[60]Zhu M,Zhao JR,Kang HP,et al.Modulation of type IIIsecretion system in Pseudomonas aeruginosa:involvement of the PA4857 gene product[J].Frontiers in Microbiology,2016,7:7
[61]R?mling U,Galperin MY,Gomelsky M.Cyclic di-GMP:the first 25 years of a universal bacterial second messenger[J].Microbiology and Molecular Biology Reviews,2013,77(1):1-52
[62]Moscoso JA,Mikkelsen H,Heeb S,et al.The Pseudomonas aeruginosa sensor RetS switches type III and type VI secretion via c-di-GMP signalling[J].Environmental Microbiology,2011,13(12):3128-3138
[63]Moscoso JA,Jaeger T,Valentini M,et al.The diguanylate cyclase SadC is a central player in Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa[J].Journal of Bacteriology,2014,196(23):4081-4088
[64]Li KW,Xu C,Jin YX,et al.SuhB is a regulator of multiple virulence genes and essential for pathogenesis of Pseudomonas aeruginosa[J].mBio,2013,4(6):e00419-13
[65]Li KW,Yang GJ,Debru AB,et al.SuhB regulates the motile-sessile switch in Pseudomonas aeruginosa through the Gac/Rsm pathway and c-di-GMP signaling[J].Frontiers in Microbiology,2017,8:1045
[66]Bhagirath AY,Somayajula D,Li YQ,et al.CmpX affects virulence in Pseudomonas aeruginosa through the Gac/Rsm signaling pathway and by modulating c-di-GMP levels[J].The Journal of Membrane Biology,2018,251(1):35-49
[67]Aragon IM,Pérez-Mendoza D,Moscoso JA,et al.Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp.infections[J].Environmental Microbiology,2015,17(11):4332-4351
[68]Rossello J,Lima A,Gil M,et al.The EAL-domain protein FcsRregulates flagella,chemotaxis and type III secretion system in Pseudomonas aeruginosa by a phosphodiesterase independent mechanism[J].Scientific Reports,2017,7(1):10281
[69]Chen GK,Zhao Q,Zhu F,et al.Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa[J].Microbiological Research,2016,188-189:90-96
[70]Abisado RG,Benomar S,Klaus JR,et al.Bacterial quorum sensing and microbial community interactions[J].mBio,2018,9(3):e02331-17
[71]Lee J,Zhang LH.The hierarchy quorum sensing network in Pseudomonas aeruginosa[J].Protein&Cell,2015,6(1):26-41
[72]Bleves S,Soscia C,Nogueira-Orlandi P,et al.Quorum sensing negatively controls type III secretion regulon expression in Pseudomonas aeruginosa PAO1[J].Journal of Bacteriology,2005,187(11):3898-3902
[73]Hogardt M,Roeder M,Schreff AM,et al.Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS[J].Microbiology,2004,150(4):843-851
[74]Kong WN,Liang HH,Shen LX,et al.Regulation of type IIIsecretion system by Rhl and PQS quorum sensing systems in Pseudomonas aeruginosa[J].Acta Microbiologica Sinica,2009,49(9):1158-1164(in Chinese)孔伟娜,梁海华,沈立新,等.铜绿假单胞菌中III型分泌系统受Rhl和PQS群体感应系统调节[J].微生物学报,2009,49(9):1158-1164
[75]Singh G,Wu B,Baek MS,et al.Secretion of Pseudomonas aeruginosa type III cytotoxins is dependent on pseudomonas quinolone signal concentration[J].Microbial Pathogenesis,2010,49(4):196-203
[76]Liang HH,Deng X,Li XF,et al.Molecular mechanisms of master regulator VqsM mediating quorum-sensing and antibiotic resistance in Pseudomonas aeruginosa[J].Nucleic Acids Research,2014,42(16):10307-10320
[77]Liang HH,Kong WN,Shen T,et al.The effect of pmpR on the type III secretion system in Pseudomonas aeruginosa[J].Chinese Science Bulletin,2012,57(19):2413-2418
[78]Allmond LR,Ajayi T,Moriyama K,et al.V-antigen genotype and phenotype analyses of clinical isolates of Pseudomonas aeruginosa[J].Journal of Clinical Microbiology,2004,42(8):3857-3860
[79]Martin DW,Schurr MJ,Mudd MH,et al.Mechanism of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients[J].Proceedings of the National Academy of Sciences of the United States of America,1993,90(18):8377-8381
[80]Wu WH,Badrane H,Arora S,et al.MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa[J].Journal of Bacteriology,2004,186(22):7575-7585
[81]Schurr MJ,Yu H,Martinez-Salazar JM,et al.Control of AlgU,a member of the sigma E-like family of stress sigma factors,by the negative regulators MucA and MucB and Pseudomonas aeruginosa conversion to mucoidy in cystic fibrosis[J].Journal of Bacteriology,1996,178(16):4997-5004
[82]Wozniak DJ,Ohman DE.Transcriptional analysis of the Pseudomonas aeruginosa genes algR,algB,and algD reveals a hierarchy of alginate gene expression which is modulated by algT[J].Journal of Bacteriology,1994,176(19):6007-6014
[83]Intile PJ,Diaz MR,Urbanowski ML,et al.The AlgZRtwo-component system recalibrates the RsmAYZposttranscriptional regulatory system to inhibit expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2014,196(2):357-366
[84]Jones AK,Fulcher NB,Balzer GJ,et al.Activation of the Pseudomonas aeruginosa AlgU regulon through mucA mutation inhibits cyclic AMP/Vfr signaling[J].Journal of Bacteriology,2010,192(21):5709-5717
[85]Aspedon A,Palmer K,Whiteley M.Microarray analysis of the osmotic stress response in Pseudomonas aeruginosa[J].Journal of Bacteriology,2006,188(7):2721-2725
[86]Wu WH,Jin SG.PtrB of Pseudomonas aeruginosa suppresses the type III secretion system under the stress of DNAdamage[J].Journal of Bacteriology,2005,187(17):6058-6068
[87]Elsen S,Ragno M,Attree I.PtrA is a periplasmic protein involved in Cu tolerance in Pseudomonas aeruginosa[J].Journal of Bacteriology,2011,193(13):3376-3378
[88]Ha UH,Kim J,Badrane H,et al.An in vivo inducible gene of Pseudomonas aeruginosa encodes an anti-ExsA to suppress the type III secretion system[J].Molecular Microbiology,2004,54(2):307-320
[89]Anderson GG,Yahr TL,Lovewell RR,et al.The Pseudomonas aeruginosa magnesium transporter MgtE inhibits transcription of the type III secretion system[J].Infection and Immunity,2010,78(3):1239-1249
[90]Chakravarty S,Melton CN,Bailin A,et al.Pseudomonas aeruginosa magnesium transporter MgtE inhibits type IIIsecretion system gene expression by stimulating rsmYZtranscription[J].Journal of Bacteriology,2017,199(23):e00268-17
[91]Chung JCS,Rzhepishevska O,Ramstedt M,et al.Type IIIsecretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is stimulated by isocitrate lyase activity[J].Open Biology,2013,3(1):120131
[92]O’Callaghan J,Reen FJ,Adams C,et al.Low oxygen induces the type III secretion system in Pseudomonas aeruginosa via modulation of the small RNAs rsmZ and rsmY[J].Microbiology,2011,157(12):3417-3428
[93]Van Alst NE,Wellington M,Clark VL,et al.Nitrite reductase NirS is required for type III secretion system expression and virulence in the human monocyte cell line THP-1 by Pseudomonas aeruginosa[J].Infection and Immunity,2009,77(10):4446-4454
[94]Barbier M,Damron FH,Bielecki P,et al.From the environment to the host:re-wiring of the transcriptome of Pseudomonas aeruginosa from 22°C to 37°C[J].PLoS One,2014,9(2):e89941
[95]Kang Y,Lunin VV,Skarina T,et al.The long-chain fatty acid sensor,PsrA,modulates the expression of rpoS and the type IIIsecretion exsCEBA operon in Pseudomonas aeruginosa[J].Molecular Microbiology,2009,73(1):120-136
[96]Shen DK,Filopon D,Kuhn L,et al.PsrA is a positive transcriptional regulator of the type III secretion system in Pseudomonas aeruginosa[J].Infection and Immunity,2006,74(2):1121-1129
[97]Dacheux D,Epaulard O,de Groot A,et al.Activation of the Pseudomonas aeruginosa type III secretion system requires an intact pyruvate dehydrogenase aceAB operon[J].Infection and Immunity,2002,70(7):3973-3977
[98]O’Callaghan J,Reen JF,Adams C,et al.A novel host-responsive sensor mediates virulence and type III secretion during Pseudomonas aeruginosa-host cell interactions[J].Microbiology,2012,158(Pt 4):1057-1070
[99]Zhou L,Wang J,Zhang LH.Modulation of bacterial type IIIsecretion system by a spermidine transporter dependent signaling pathway[J].PLoS One,2007,2(12):e1291
[100]Linares JF,López JA,Camafeita E,et al.Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa[J].Journal of Bacteriology,2005,187(4):1384-1391
[101]Rietsch A,Wolfgang MC,Mekalanos JJ.Effect of metabolic imbalance on expression of type III secretion genes in Pseudomonas aeruginosa[J].Infection and Immunity,2004,72(3):1383-1390
[102]Dong YH,Zhang XF,Zhang LH.The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa[J].MicrobiologyOpen,2013,2(1):161-172
[103]Yeung ATY,Bains M,Hancock REW.The sensor kinase CbrAis a global regulator that modulates metabolism,virulence,and antibiotic resistance in Pseudomonas aeruginosa[J].Journal of Bacteriology,2011,193(4):918-931
[104]Shen DK,Filopon D,Chaker H,et al.High-cell-density regulation of the Pseudomonas aeruginosa type III secretion system:implications for tryptophan catabolites[J].Microbiology,2008,154(8):2195-2208
[105]Mou R,Du X,Wang XH,et al.Pseudomonas aeruginosa gene pfm affects the expression levels of type III secretion system effectors[J].Microbiology China,2013,40(8):1462-1467(in Chinese)牟锐,杜星,王雪涵,等.铜绿假单胞菌pfm基因对三型分泌系统效应蛋白的影响[J].微生物学通报,2013,40(8):1462-1467
[106]Neidig A,Yeung ATY,Rosay T,et al.TypA is involved in virulence,antimicrobial resistance and biofilm formation in Pseudomonas aeruginosa[J].BMC Microbiology,2013,13:77
[107]McCarthy RR,Mooij MJ,Reen FJ,et al.A new regulator of pathogenicity(bvlR)is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa[J].Microbiology,2014,160(Pt 7):1488-1500
[108]Intile PJ,Balzer GJ,Wolfgang MC,et al.The RNA helicase DeaD stimulates ExsA translation to promote expression of the Pseudomonas aeruginosa type III secretion system[J].Journal of Bacteriology,2015,197(16):2664-2674
[109]Wang BB,Li B,Liang Y,et al.Pleiotropic effects of temperature-regulated 2-OH-lauroytransferase(PA0011)on Pseudomonas aeruginosa antibiotic resistance,virulence and type III secretion system[J].Microbial Pathogenesis,2016,91:5-17
[110]Chen RH,Weng YD,Zhu F,et al.Polynucleotide phosphorylase regulates multiple virulence factors and the stabilities of small RNAs RsmY/Z in Pseudomonas aeruginosa[J].Frontiers in Microbiology,2016,7:247
[111]Li M,Long YQ,Liu Y,et al.HigB of Pseudomonas aeruginosa enhances killing of phagocytes by up-regulating the type IIIsecretion system in ciprofloxacin induced persister cells[J].Frontiers in Cellular and Infection Microbiology,2016,6:125
[112]Pérez-Gallego M,Torrens G,Castillo-Vera J,et al.Impact of AmpC derepression on fitness and virulence:the mechanism or the pathway?[J].mBio,2016,7(5):e01783-16
[113]Deng X,Li M,Pan XL,et al.Fis regulates type III secretion system by influencing the transcription of exsA in Pseudomonas aeruginosa strain PA14[J].Frontiers in Microbiology,2017,8:669
[114]Zhang YF,Han K,Chandler CE,et al.Probing the sRNAregulatory landscape of P.aeruginosa:post-transcriptional control of determinants of pathogenicity and antibiotic susceptibility[J].Molecular Microbiology,2017,106(6):919-937
[115]Anantharajah A,Mingeot-Leclercq MP,Bambeke F.Targeting the type three secretion system in Pseudomonas aeruginosa[J].Trends in Pharmacological Sciences,2016,37(9):734-749
[116]Yamazaki A,Li J,Zeng Q,et al.Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system[J].Antimicrobial Agents and Chemotherapy,2012,56(1):36-43
[117]Shan JM,Wu XG,Yuan XC,et al.The influence of cinnamic acid derivatives on the type III secretion system of Pseudomonas aeruginosa PAO1[J].Microbiology China,2014,41(10):2061-2069(in Chinese)单金明,吴小刚,袁小琛,等.肉桂酸衍生物对铜绿假单胞菌PAO1 III型分泌系统的影响[J].微生物学通报,2014,41(10):2061-2069
[118]Grier MC,Garrity-Ryan LK,Bartlett VJ,et al.N-hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa:in vitro anti-virulence activity and metabolic stability[J].Bioorganic&Medicinal Chemistry Letters,2010,20(11):3380-3383
[119]Marsden AE,King JM,Spies MA,et al.Inhibition of Pseudomonas aeruginosa ExsA DNA-binding activity by N-hydroxybenzimidazoles[J].Antimicrobial Agents and Chemotherapy,2016,60(2):766-776
[120]Wang D,Zetterstrom CE,Gabrielsen M,et al.Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds[J].Journal of Biological Chemistry,2011,286(34):29922-29931
[121]Enquist PA,Gylfe?,H?gglund U,et al.Derivatives of8-hydroxyquinoline-antibacterial agents that target intra-and extracellular Gram-negative pathogens[J].Bioorganic&Medicinal Chemistry Letters,2012,22(10):3550-3553
[122]Felise HB,Nguyen HV,Pfuetzner RA,et al.An inhibitor of gram-negative bacterial virulence protein secretion[J].Cell Host&Microbe,2008,4(4):325-336
[123]Aiello D,Williams JD,Majgier-Baranowska H,et al.Discovery and characterization of inhibitors of Pseudomonas aeruginosa type III secretion[J].Antimicrobial Agents and Chemotherapy,2010,54(5):1988-1999
[124]Zhang CF,Wu XG,Li Y,et al.Synthesis and bioactivity of novel inhibitors for type III secretion system of Pseudomonas aeruginosa PAO1[J].Chinese Journal of Organic Chemistry,2013,33(6):1309-1318(in Chinese)张成芳,吴小刚,李燕,等.铜绿假单胞菌PAO1 III型分泌系统新型抑制剂的合成和生物活性研究[J].有机化学,2013,33(6):1309-1318
[125]Gu LL,Wu XG,Yuan XC,et al.Regulation of type III secretion system inhibitors on virulence factors of Pseudomonas aeruginosa PAO1[J].Microbiology China,2014,41(11):2318-2324(in Chinese)顾玲玲,吴小刚,袁小琛,等.III型分泌系统抑制剂对铜绿假单胞菌PAO1毒性因子的影响[J].微生物学通报,2014,41(11):2318-2324
[126]Frank DW,Vallis A,Wiener-Kronish JP,et al.Generation and characterization of a protective monoclonal antibody to Pseudomonas aeruginosa PcrV[J].The Journal of Infectious Diseases,2002,186(1):64-73
[127]Imamura Y,Yanagihara K,Fukuda Y,et al.Effect of anti-PcrVantibody in a murine chronic airway Pseudomonas aeruginosa infection model[J].European Respiratory Journal,2007,29(5):965-968
[128]Sawa T,Yahr TL,Ohara M,et al.Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury[J].Nature Medicine,1999,5(4):392-398
[129]Lynch SV,Flanagan JL,Sawa T,et al.Polymorphisms in the Pseudomonas aeruginosa type III secretion protein,PcrV-implications for anti-PcrV immunotherapy[J].Microbial Pathogenesis,2010,48(6):197-204
[130]DiGiandomenico A,Keller AE,Gao CH,et al.Amultifunctional bispecific antibody protects against Pseudomonas aeruginosa[J].Science Translational Medicine,2014,6(262):262ra155
[131]Fran?ois B,Luyt CE,Dugard A,et al.Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized with Pseudomonas aeruginosa:a randomized,double-blind,placebo-controlled trial[J].Critical Care Medicine,2012,40(8):2320-2326
[132]Arnoldo A,Curak J,Kittanakom S,et al.Identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme Susing a yeast phenotypic screen[J].PLoS Genetics,2008,4(2):e1000005
[133]Lee VT,Pukatzki S,Sato H,et al.Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU[J].Infection and Immunity,2007,75(3):1089-1098
[134]Kim D,Baek J,Song J,et al.Identification of arylsulfonamides as ExoU inhibitors[J].Bioorganic&Medicinal Chemistry Letters,2014,24(16):3823-3825