病原细菌受体介导的c-di-GMP信号传导及其调控机制
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摘要
细菌第二信使环二鸟苷酸(c-di-GMP)信号网络系统主要涉及信号代谢、识别、接受、传递、功能表达和调控。c-di-GMP胞内水平受到鸟苷酸环化酶(DGC)和磷酸二酯酶(PDE)的控制。c-di-GMP信号受体类型多样,包括转录调控因子、PilZ结构域蛋白、退化的GGDEF和EAL结构域蛋白、核糖体开关、多核苷酸磷酸化酶和新发现的蛋白激酶等。c-di-GMP受体接受信号后,可以在转录、翻译以及翻译后水平上对下游靶标进行调控,从而影响细菌的毒性、运动性、生物膜形成、细胞分裂等生理生化过程。本文结合本实验室对水稻白叶枯病菌的研究结果,综述了近年来国内外在c-di-GMP信号受体介导的调控机制等方面的研究进展。
The bacterial second message c-di-GMP signaling pathways mainly involve signal metabolism,signal recognition by receptor,reception and transduction,and phenotype expression and regulation.The intracellular level of c-di-GMP is precisely controlled by diguanylate cyclases(DGC)and phosphodiesterase(PDE)via biosynthesis or degradation,respectively.Several c-di-GMP receptors have been identified and characterized from various bacterial species,including transcription regulator,PilZ-domain protein,degenerate GGDEF or EAL domain protein,polynucleotide phosphorylase(PNPase),riboswitch and kinase,etc.The c-di-GMP receptors exert their regulatory functions at the transcription,translation,and post-translation levels,and regulate multiple bacterial properties including virulence,biofilm formation,motility and cell division.The recent progresses in c-di-GMP receptor-mediated regulation of bacterial behaviors were here reviewed,in combination with some of our findings on the bacterial blight pathogen of rice Xanthomonas oryzae pv.oryzae.
The bacterial second message c-di-GMP signaling pathways mainly involve signal metabolism,signal recognition by receptor,reception and transduction,and phenotype expression and regulation.The intracellular level of c-di-GMP is precisely controlled by diguanylate cyclases(DGC)and phosphodiesterase(PDE)via biosynthesis or degradation,respectively.Several c-di-GMP receptors have been identified and characterized from various bacterial species,including transcription regulator,PilZ-domain protein,degenerate GGDEF or EAL domain protein,polynucleotide phosphorylase(PNPase),riboswitch and kinase,etc.The c-di-GMP receptors exert their regulatory functions at the transcription,translation,and post-translation levels,and regulate multiple bacterial properties including virulence,biofilm formation,motility and cell division.The recent progresses in c-di-GMP receptor-mediated regulation of bacterial behaviors were here reviewed,in combination with some of our findings on the bacterial blight pathogen of rice Xanthomonas oryzae pv.oryzae.
引文
[1]Hengge R,Grundling A,Jenal U,et al.Bacterial signal transduction by c-di-GMP and other nucleotide second messengers[J].Journal of Bacteriology,2016,198:15-26.
[2]Ross P,Weinhouse H,Aloni Y,et al.Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid[J].Nature,1987,325:279-281.
[3]Romling U,Gomelsky M,Galperin M Y.C-di-GMP:the dawning of a novel bacterial signalling system[J].Molecular Microbiology,2005,57:629-639.
[4]Hengge R.Principles of c-di-GMP signalling in bacteria[J].Nature Reviews Microbiology,2009,7:263-273.
[5]Romling U,Galperin M Y,Gomelsky M.Cyclic di-GMP:the first25years of a universal bacterial second messenger[J].Microbiology and Molecular Biology Reviews,2013,77(1):1-52.
[6]Sondermann H,Shikuma N J,Yildiz FH.You’ve come a long way:c-di-GMP signaling[J].Current Opinion in Microbiology,2012,15:140-146.
[7]Schirmer T,Jenal U.Structural and mechanistic determinants of c-di-GMP signalling[J].Nature Reviews Microbiology,2009,7(10):724-735.
[8]Bordeleau E,Fortier L C,Malouin F,et al.c-di-GMP turnover in Clostridium difficile is controlled by aplethora of diguanylate cyclases and phosphodiesterases[J].PLoS Genetics,2011,7:e1002039.
[9]Simm R,Morr M,Kader A,et al.GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility[J].Molecular Microbiology,2004,53:1123-1134.
[10]Paul R,Abel S,Wassmann P,et al.Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization[J].The Journal of Biological Chemistry,2007,282:29170-29177.
[11]Goymer P,Kahn S G,Malone J G,et al.Adaptive divergence in experimental populations of Pseudomonas fluorescens II.Role of the GGDEF regulator WspR in evolution and development of the wrinkly spreader phenotype[J].Genetics,2006,173(2):89-99.
[12]Aragon I M,Perez-Mendoza D,Moscoso J A,et al.Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp.infections[J].Environmental Microbiology,2015,17(11):4332-4351.
[13]Dey A K,Bhagat A,Chowdhury R.Host cell contact induces expression of virulence factors and VieA,a cyclic di-GMP phosphodiesterase in Vibrio cholerae[J].Journal of Bacteriology,2013,195:2004-2010.
[14]Roy A B,Petrova O E,Sauer K.The phosphodiesterase DipA(PA5017)is essential for Pseudomonas aeruginosa biofilm dispersion[J].Journal of Bacteriology,2012,194:2904-2915.
[15]Yang Fenghuan,Tian Fang,Sun Lei,et al.A novel two-component system PdeK/PdeR regulates c-di-GMP turnover and virulence of Xanthomonas oryzae pv.oryzae[J].Molecular Plant-Microbe Interactions,2012,25(10):1361-1369.
[16]Chou S H,Galperin M Y.Diversity of c-di-GMP-binding proteins and mechanisms[J].Journal of Bacteriology,2015,doi:10.1128/JB.00333-15.
[17]Hickman J W,Harwood C S.Identification of FleQ fromPseudomonas aeruginosa as a c-di-GMP-responsive transcription factor[J].Molecular Microbiology,2008,69(2):376-389.
[18]Jonas K,Melefors O,Romling U.Regulation of c-di-GMP metabolism in biofilms[J].Future Microbiology,2009,4(3):341-358.
[19]Krasteva P V,Fong J C,Shikuma N J,et al.Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP[J].Science,2010,327:866-868.
[20]Wilksch J J,Yang J,Clements A,et al.MrkH,a novel c-diGMP-dependent transcriptional activator,controls Klebsiella pneumoniae biofilm formation by regulating type 3fimbriae expression[J].PLoS Pathogens,2011,7:e1002204.
[21]Yang J,Wilksch J J,Tan J W,et al.Transcriptional activation of the mrkA promoter of the Klebsiella pneumoniae type 3fimbrial operon by the c-di-GMP-dependent MrkH protein[J].PLoS ONE,2013,8:e79038.
[22]Tan J W,Wilksch J J,Hocking D M,et al.Positive autoregulation of mrkHI by the cyclic di-GMP-dependent MrkH protein in the biofilm regulatory circuit of Klebsiella pneumoniae[J].Journal of Bacteriology,2015,197:1659-1667.
[23]Fazli M,O’Connell A,Nilsson M,et al.The CRP/FNR family protein Bcam1349is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia[J].Molecular Microbiology,2011,82:327-341.
[24]管文静,吴茂森,何晨阳.水稻白叶枯病菌核苷酸信号受体蛋白Clpxoo的分子鉴定及其功能分析[J].微生物学报,2009,49(1):32-37.
[25]李波,田芳,陈华民,等.c-di-GMP抑制转录调控因子Clpxoo与葡聚糖酶基因启动子的结合[J].微生物学报,2013,53(11):1116-1171.
[26]Amikam D,Galperin M Y.PilZ domain is part of the bacterial c-diGMP binding protein[J].Bioinformatics,2006,22(1):3-6.
[27]Ryjenkov D A,Simm R,Romling U,et al.The PilZ domain is a receptor for the second messenger c-di-GMP:the PilZ domain protein YcgR controls motility in enterobacteria[J].The Journal of Biological Chemistry,2006,281(41):30310-30314.
[28]Merighi M,Lee V T,Hyodo M,et al.The second messenger bis-(3′-5′)-cyclic-GMP and its PilZ domain-containing receptor Alg44are required for alginate biosynthesis in Pseudomonas aeruginosa[J].Molecular Microbiology,2007,65(4):876-895.
[29]Whitney J C,Whitfield G B,Marmont L S,et al.Dimeric cdi-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa[J].The Journal of Biological Chemistry,2015,290:12451-12462.
[30]Pratt J T,Tamayo R,Tischler A D,et al.PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae[J].The Journal of Biological Chemistry,2007,282(17):12860-12870.
[31]Yang Fenghuan,Tian Fang,Chen Huamin,et al.The Xanthomonas oryzae pv.oryzae PilZ-domain proteins function differentially in cyclic di-GMP binding,and regulation of virulence and motility[J].Applied and Enviromental Microbiology,2015,81(13):4358-4367.
[32]Ozaki S,Schalch-Moser A,Zumthor L,et al.Activation and polar sequestration of PopA,a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control[J].Molecular Microbiology,2014,94:580-594.
[33]Beyhan S,Odell L S,Yildiz F H.Identification and characterization of cyclic diguanylate signaling systems controlling rugosity in Vibrio cholerae[J].Journal of Bacteriology,2008,190:7392-7405.
[34]Fang X,Ahmad I,Blanka A,et al.GIL,a new c-di-GMPbinding protein domain involved in regulation of cellulose synthesis in enterobacteria[J].Molecular Microbiology,2014,93:439-452.
[35]Newell P D,Monds R D,O’Toole G A.LapD is a bis-cyclic dimeric GMP-binding protein that regulates surface attachment by Pseudomonas fluorescens Pf0-1[J].Proceedings of the National Academy of Sciences of the United States of America,2009,106:3461-3466.
[36]Guzzo C R,Salinas R K,Andrade M O,et al.PILZ protein structure and interactions with PILB and the FIMX EAL domain:implications for control of type IV pilus biogenesis[J].Journal of Molecular Biology,2009,393(4):848-866.
[37]Guzzo C R,Dunger G,Salinas R K,et al.Structure of the PilZ-FimXEAL-c-di-GMP complex responsible for the regulation of bacterial Type IV pilus biogenesis[J].Journal of Molecular Biology,2013,425(12):2174-2197.
[38]Navarro M V,De N,Bae N,et al.Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX[J].Structure,2009,17(8):1104-1116.
[39]Yang Fenghuan,Tian Fang,Li Xiaotong,et al.The degenerate EAL-GGDEF domain protein Filp functions as a cyclic di-GMP receptor and specifically interacts with the PilZ-domain protein PXO_02715to regulate virulence in Xanthomonas oryzae pv.oryzae[J].Molecular Plant-Microbe Interactions,2014,6(27):578-589.
[40]Lee E R,Baker J L,Weinberg Z,et al.An allosteric self-splicing ribozyme triggered by a bacterial second messenger[J].Science,2010,329(5993):845-848.
[41]Smith K D,Lipchock S V,Livingston A L,et al.Structural and biochemical determinants of ligand binding by the c-diGMP riboswitch[J].Biochemistry,2010,49:7351-7359.
[42]Smith K D,Lipchock SV,Ames TD,et al.Structural basis of ligand binding by a c-di-GMP riboswitch[J].Nature Structural&Molecular Biology,2009,16:1218-1223.
[43]Bordeleau E,Purcell E B,Lafontaine D A,et al.Cyclic diGMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile[J].Journal of Bacteriology,2015,197:819-832.
[44]Tuckerman J R,Gonzalez G,Gilles-Gonzalez M A,et al.Cyclic di-GMP activation of polynucleotide phosphorylase signaldependent RNA processing[J].Journal of Molecular Biology,2011,407(5):633-639.
[45]Wang Y C,Chin K H,Chuah M L,et al.Crystallization and preliminary X-ray diffraction studies of Xanthomonas campestris PNPase in the presence of c-di-GMP[J].Acta Crystallographica Section F,2012,68(10):1247-1250.
[46]Lori C,Ozaki S,Steiner S,et al.Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication[J].Nature,2015,523(7559):236-239.
[47]Tsokos C G,Perchuk B S,Laub M T.A dynamic complex of signaling proteins uses polar localization to regulate cell-fate a symmetry in Caulobacter crescentus[J].Developmental Cell,2011,20(3):329-341.
[48]Barnhart D M,Su S,Farrand S K.A signaling pathway involving the diguanylate cyclase CelR and the response regulator DivK controls cellulose synthesis in Agrobacterium tumefaciens[J].Journal of Bacteriology,2014,196:1257-1274.
[2]Ross P,Weinhouse H,Aloni Y,et al.Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid[J].Nature,1987,325:279-281.
[3]Romling U,Gomelsky M,Galperin M Y.C-di-GMP:the dawning of a novel bacterial signalling system[J].Molecular Microbiology,2005,57:629-639.
[4]Hengge R.Principles of c-di-GMP signalling in bacteria[J].Nature Reviews Microbiology,2009,7:263-273.
[5]Romling U,Galperin M Y,Gomelsky M.Cyclic di-GMP:the first25years of a universal bacterial second messenger[J].Microbiology and Molecular Biology Reviews,2013,77(1):1-52.
[6]Sondermann H,Shikuma N J,Yildiz FH.You’ve come a long way:c-di-GMP signaling[J].Current Opinion in Microbiology,2012,15:140-146.
[7]Schirmer T,Jenal U.Structural and mechanistic determinants of c-di-GMP signalling[J].Nature Reviews Microbiology,2009,7(10):724-735.
[8]Bordeleau E,Fortier L C,Malouin F,et al.c-di-GMP turnover in Clostridium difficile is controlled by aplethora of diguanylate cyclases and phosphodiesterases[J].PLoS Genetics,2011,7:e1002039.
[9]Simm R,Morr M,Kader A,et al.GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility[J].Molecular Microbiology,2004,53:1123-1134.
[10]Paul R,Abel S,Wassmann P,et al.Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization[J].The Journal of Biological Chemistry,2007,282:29170-29177.
[11]Goymer P,Kahn S G,Malone J G,et al.Adaptive divergence in experimental populations of Pseudomonas fluorescens II.Role of the GGDEF regulator WspR in evolution and development of the wrinkly spreader phenotype[J].Genetics,2006,173(2):89-99.
[12]Aragon I M,Perez-Mendoza D,Moscoso J A,et al.Diguanylate cyclase DgcP is involved in plant and human Pseudomonas spp.infections[J].Environmental Microbiology,2015,17(11):4332-4351.
[13]Dey A K,Bhagat A,Chowdhury R.Host cell contact induces expression of virulence factors and VieA,a cyclic di-GMP phosphodiesterase in Vibrio cholerae[J].Journal of Bacteriology,2013,195:2004-2010.
[14]Roy A B,Petrova O E,Sauer K.The phosphodiesterase DipA(PA5017)is essential for Pseudomonas aeruginosa biofilm dispersion[J].Journal of Bacteriology,2012,194:2904-2915.
[15]Yang Fenghuan,Tian Fang,Sun Lei,et al.A novel two-component system PdeK/PdeR regulates c-di-GMP turnover and virulence of Xanthomonas oryzae pv.oryzae[J].Molecular Plant-Microbe Interactions,2012,25(10):1361-1369.
[16]Chou S H,Galperin M Y.Diversity of c-di-GMP-binding proteins and mechanisms[J].Journal of Bacteriology,2015,doi:10.1128/JB.00333-15.
[17]Hickman J W,Harwood C S.Identification of FleQ fromPseudomonas aeruginosa as a c-di-GMP-responsive transcription factor[J].Molecular Microbiology,2008,69(2):376-389.
[18]Jonas K,Melefors O,Romling U.Regulation of c-di-GMP metabolism in biofilms[J].Future Microbiology,2009,4(3):341-358.
[19]Krasteva P V,Fong J C,Shikuma N J,et al.Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP[J].Science,2010,327:866-868.
[20]Wilksch J J,Yang J,Clements A,et al.MrkH,a novel c-diGMP-dependent transcriptional activator,controls Klebsiella pneumoniae biofilm formation by regulating type 3fimbriae expression[J].PLoS Pathogens,2011,7:e1002204.
[21]Yang J,Wilksch J J,Tan J W,et al.Transcriptional activation of the mrkA promoter of the Klebsiella pneumoniae type 3fimbrial operon by the c-di-GMP-dependent MrkH protein[J].PLoS ONE,2013,8:e79038.
[22]Tan J W,Wilksch J J,Hocking D M,et al.Positive autoregulation of mrkHI by the cyclic di-GMP-dependent MrkH protein in the biofilm regulatory circuit of Klebsiella pneumoniae[J].Journal of Bacteriology,2015,197:1659-1667.
[23]Fazli M,O’Connell A,Nilsson M,et al.The CRP/FNR family protein Bcam1349is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia[J].Molecular Microbiology,2011,82:327-341.
[24]管文静,吴茂森,何晨阳.水稻白叶枯病菌核苷酸信号受体蛋白Clpxoo的分子鉴定及其功能分析[J].微生物学报,2009,49(1):32-37.
[25]李波,田芳,陈华民,等.c-di-GMP抑制转录调控因子Clpxoo与葡聚糖酶基因启动子的结合[J].微生物学报,2013,53(11):1116-1171.
[26]Amikam D,Galperin M Y.PilZ domain is part of the bacterial c-diGMP binding protein[J].Bioinformatics,2006,22(1):3-6.
[27]Ryjenkov D A,Simm R,Romling U,et al.The PilZ domain is a receptor for the second messenger c-di-GMP:the PilZ domain protein YcgR controls motility in enterobacteria[J].The Journal of Biological Chemistry,2006,281(41):30310-30314.
[28]Merighi M,Lee V T,Hyodo M,et al.The second messenger bis-(3′-5′)-cyclic-GMP and its PilZ domain-containing receptor Alg44are required for alginate biosynthesis in Pseudomonas aeruginosa[J].Molecular Microbiology,2007,65(4):876-895.
[29]Whitney J C,Whitfield G B,Marmont L S,et al.Dimeric cdi-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa[J].The Journal of Biological Chemistry,2015,290:12451-12462.
[30]Pratt J T,Tamayo R,Tischler A D,et al.PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae[J].The Journal of Biological Chemistry,2007,282(17):12860-12870.
[31]Yang Fenghuan,Tian Fang,Chen Huamin,et al.The Xanthomonas oryzae pv.oryzae PilZ-domain proteins function differentially in cyclic di-GMP binding,and regulation of virulence and motility[J].Applied and Enviromental Microbiology,2015,81(13):4358-4367.
[32]Ozaki S,Schalch-Moser A,Zumthor L,et al.Activation and polar sequestration of PopA,a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control[J].Molecular Microbiology,2014,94:580-594.
[33]Beyhan S,Odell L S,Yildiz F H.Identification and characterization of cyclic diguanylate signaling systems controlling rugosity in Vibrio cholerae[J].Journal of Bacteriology,2008,190:7392-7405.
[34]Fang X,Ahmad I,Blanka A,et al.GIL,a new c-di-GMPbinding protein domain involved in regulation of cellulose synthesis in enterobacteria[J].Molecular Microbiology,2014,93:439-452.
[35]Newell P D,Monds R D,O’Toole G A.LapD is a bis-cyclic dimeric GMP-binding protein that regulates surface attachment by Pseudomonas fluorescens Pf0-1[J].Proceedings of the National Academy of Sciences of the United States of America,2009,106:3461-3466.
[36]Guzzo C R,Salinas R K,Andrade M O,et al.PILZ protein structure and interactions with PILB and the FIMX EAL domain:implications for control of type IV pilus biogenesis[J].Journal of Molecular Biology,2009,393(4):848-866.
[37]Guzzo C R,Dunger G,Salinas R K,et al.Structure of the PilZ-FimXEAL-c-di-GMP complex responsible for the regulation of bacterial Type IV pilus biogenesis[J].Journal of Molecular Biology,2013,425(12):2174-2197.
[38]Navarro M V,De N,Bae N,et al.Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX[J].Structure,2009,17(8):1104-1116.
[39]Yang Fenghuan,Tian Fang,Li Xiaotong,et al.The degenerate EAL-GGDEF domain protein Filp functions as a cyclic di-GMP receptor and specifically interacts with the PilZ-domain protein PXO_02715to regulate virulence in Xanthomonas oryzae pv.oryzae[J].Molecular Plant-Microbe Interactions,2014,6(27):578-589.
[40]Lee E R,Baker J L,Weinberg Z,et al.An allosteric self-splicing ribozyme triggered by a bacterial second messenger[J].Science,2010,329(5993):845-848.
[41]Smith K D,Lipchock S V,Livingston A L,et al.Structural and biochemical determinants of ligand binding by the c-diGMP riboswitch[J].Biochemistry,2010,49:7351-7359.
[42]Smith K D,Lipchock SV,Ames TD,et al.Structural basis of ligand binding by a c-di-GMP riboswitch[J].Nature Structural&Molecular Biology,2009,16:1218-1223.
[43]Bordeleau E,Purcell E B,Lafontaine D A,et al.Cyclic diGMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile[J].Journal of Bacteriology,2015,197:819-832.
[44]Tuckerman J R,Gonzalez G,Gilles-Gonzalez M A,et al.Cyclic di-GMP activation of polynucleotide phosphorylase signaldependent RNA processing[J].Journal of Molecular Biology,2011,407(5):633-639.
[45]Wang Y C,Chin K H,Chuah M L,et al.Crystallization and preliminary X-ray diffraction studies of Xanthomonas campestris PNPase in the presence of c-di-GMP[J].Acta Crystallographica Section F,2012,68(10):1247-1250.
[46]Lori C,Ozaki S,Steiner S,et al.Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication[J].Nature,2015,523(7559):236-239.
[47]Tsokos C G,Perchuk B S,Laub M T.A dynamic complex of signaling proteins uses polar localization to regulate cell-fate a symmetry in Caulobacter crescentus[J].Developmental Cell,2011,20(3):329-341.
[48]Barnhart D M,Su S,Farrand S K.A signaling pathway involving the diguanylate cyclase CelR and the response regulator DivK controls cellulose synthesis in Agrobacterium tumefaciens[J].Journal of Bacteriology,2014,196:1257-1274.