从效应蛋白视角看革兰氏阴性细菌Ⅵ型蛋白分泌系统底物转运机理
|
摘要
蛋白质分泌系统是细菌与外界交流的重要工具。革兰氏阴性细菌的Ⅵ型蛋白分泌系统(T6SS)可以转运分泌蛋白至细菌和真核细胞内,在菌间竞争中发挥重要作用,是细菌的一种重要的生存适应性武器。分泌蛋白主要包括起到运载作用的结构蛋白和有细胞毒性的效应蛋白这两类。本文主要从效应蛋白的视角讨论T6SS如何识别并转运效应蛋白的作用机理,回顾了以VgrG和PAAR为端部载体蛋白的转运途径、依赖端部运输的效应蛋白、T6SS伴侣蛋白等重要发现的背景和过程,并综述了T6SS分泌途径的新进展。
Protein secretion systems are crucial tools that microbes use to interact with their surroundingenvironment. The type Ⅵ protein secretion system(T6 SS) is widely distributed in Gram-negative bacteriaand capable of delivering effector to both eukaryotic and prokaryotic cells. Here we discuss, from effectorstudy perspective, the mechanism of substrate recognition and translocation by T6 SS, focusing on the keydiscoveries of VgrG-PAAR(Proline-Alanine-Alanine-aRginine) dependent secretion pathway, and itscognate effectors and chaperone proteins.
Protein secretion systems are crucial tools that microbes use to interact with their surroundingenvironment. The type Ⅵ protein secretion system(T6 SS) is widely distributed in Gram-negative bacteriaand capable of delivering effector to both eukaryotic and prokaryotic cells. Here we discuss, from effectorstudy perspective, the mechanism of substrate recognition and translocation by T6 SS, focusing on the keydiscoveries of VgrG-PAAR(Proline-Alanine-Alanine-aRginine) dependent secretion pathway, and itscognate effectors and chaperone proteins.
引文
[1]Chassaing B,Cascales E.Antibacterial weapons:targeted destruction in the microbiota[J].Trends in Microbiology,2018,26(4):329-338
[2]Aoki SK,Pamma R,Hernday AD,et al.Contact-dependent inhibition of growth in Escherichia coli[J].Science,2005,309(5738):1245-1248
[3]Pukatzki S,Ma AT,Sturtevant D,et al.Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(5):1528-1533
[4]Mougous JD,Cuff ME,Raunser S,et al.A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus[J].Science,2006,312(5779):1526-1530
[5]Ho BT,Dong TG,Mekalanos JJ.A view to a kill:the bacterial type VI secretion system[J].Cell Host&Microbe,2014,15(1):9-21
[6]Basler M.Type VI secretion system:secretion by a contractile nanomachine[J].Philosophical Transactions of the Royal Society of London.Series B,Biological Sciences,2015,370(1679):20150021
[7]Brackmann M,Nazarov S,Wang J,et al.Using force to punch holes:mechanics of contractile nanomachines[J].Trends in Cell Biology,2017,27(9):623-632
[8]Taylor NMI,van Raaij MJ,Leiman PG.Contractile injection systems of bacteriophages and related systems[J].Molecular Microbiology,2018,108(1):6-15
[9]van Son Nguyen,Logger L,Spinelli S,et al.Type VI secretion TssK baseplate protein exhibits structural similarity with phage receptor-binding proteins and evolved to bind the membrane complex[J].Nature Microbiology,2017,2:17103
[10]Leiman PG,Basler M,Ramagopal UA,et al.Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin[J].Proceedings of the National Academy of Sciences of the United States of America,2009,106(11):4154-4159
[11]Shneider MM,Buth SA,Ho BT,et al.PAAR-repeat proteins sharpen and diversify the type VI secretion system spike[J].Nature,2013,500(7462):350-353
[12]Kapitein N,B?nemann G,Pietrosiuk A,et al.ClpV recycles VipA/VipB tubules and prevents non-productive tubule formation to ensure efficient type VI protein secretion[J].Molecular Microbiology,2013,87(5):1013-1028
[13]B?nemann G,Pietrosiuk A,Diemand A,et al.Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion[J].The EMBO Journal,2009,28(4):315-325
[14]Basler M,Mekalanos JJ.Type 6 secretion dynamics within and between bacterial cells[J].Science,2012,337(6096):815
[15]Dong TG,Mekalanos JJ.Characterization of the RpoN regulon reveals differential regulation of T6SS and new flagellar operons in Vibrio cholerae O37 strain V52[J].Nucleic Acids Research,2012,40(16):7766-7775
[16]Zoued A,Durand E,Brunet YR,et al.Priming and polymerization of a bacterial contractile tail structure[J].Nature,2016,531(7592):59-63
[17]Santin YG,Doan T,Lebrun R,et al.In vivo TssA proximity labelling during type VI secretion biogenesis reveals TagA as a protein that stops and holds the sheath[J].Nature Microbiology,2018,3(11):1304-1313
[18]Nazarov S,Schneider JP,Brackmann M,et al.Cryo-EMreconstruction of Type VI secretion system baseplate and sheath distal end[J].The EMBO Journal,2018,37(4):e97103
[19]Wang J,Brackmann M,Casta?o-Díez D,et al.Cryo-EM structure of the extended type VI secretion system sheath-tube complex[J].Nature Microbiology,2017,2(11):1507-1512
[20]Hood RD,Singh P,Hsu F,et al.A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria[J].Cell Host&Microbe,2010,7(1):25-37
[21]Dong TG,Dong S,Catalano C,et al.Generation of reactive oxygen species by lethal attacks from competing microbes[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(7):2181-2186
[22]Russell AB,Peterson SB,Mougous JD.Type VI secretion system effectors:poisons with a purpose[J].Nature Reviews Microbiology,2014,12(2):137-148
[23]Pukatzki S,Ma AT,Revel AT,et al.Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(39):15508-15513
[24]Dong TG,Ho BT,Yoder-Himes DR,et al.Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(7):2623-2628
[25]Zheng J,Ho B,Mekalanos JJ.Genetic analysis of anti-amoebae and anti-bacterial activities of the type VI secretion system in Vibrio cholerae[J].PLoS One,2011,6(8):e23876
[26]Ma JL,Pan ZH,Huang JH,et al.The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems[J].Virulence,2017,8(7):1189-1202
[27]Filloux A,Hachani A,Bleves S.The bacterial type VI secretion machine:yet another player for protein transport across membranes[J].Microbiology,2008,154:1570-1583
[28]Pukatzki S,McAuley SB,Miyata ST.The type VI secretion system:translocation of effectors and effector-domains[J].Current Opinion in Microbiology,2009,12(1):11-17
[29]Ma AT,McAuley S,Pukatzki S,et al.Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells[J].Cell Host&Microbe,2009,5(3):234-243
[30]Zheng J,Leung KY.Dissection of a type VI secretion system in Edwardsiella tarda[J].Molecular Microbiology,2007,66(5):1192-1206
[31]Silverman JM,Agnello DM,Zheng HJ,et al.Haemolysin coregulated protein is an exported receptor and chaperone of Type VI secretion substrates[J].Molecular Cell,2013,51(5):584-593
[32]Russell AB,Singh P,Brittnacher M,et al.A widespread bacterial type VI secretion effector superfamily identified using a heuristic approach[J].Cell Host&Microbe,2012,11(5):538-549
[33]Mac Intyre DL,Miyata ST,Kitaoka M,et al.The Vibrio cholerae type VI secretion system displays antimicrobial properties[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(45):19520-19524
[34]Li M,Le Trong I,Carl MA,et al.Structural basis for type VIsecretion effector recognition by a cognate immunity protein[J].PLoS Pathogens,2012,8(4):e1002613
[35]Liang XY,Moore R,Wilton M,et al.Identification of divergent type VI secretion effectors using a conserved chaperone domain[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(29):9106-9111
[36]Hachani A,Allsopp LP,Oduko Y,et al.The VgrG proteins are“àla carte”delivery systems for bacterial type VI effectors[J].The Journal of Biological Chemistry,2014,289(25):17872-17884
[37]Bondage DD,Lin JS,Ma LS,et al.VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor-effector complex[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(27):E3931-E3940
[38]Flaugnatti N,Le TTH,Canaan S,et al.A phospholipase A1antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery[J].Molecular Microbiology,2016,99(6):1099-1118
[39]Unterweger D,Kostiuk B,?tjengerdes R,et al.Chimeric adaptor proteins translocate diverse type VI secretion system effectors in Vibrio cholerae[J].The EMBO Journal,2015,34(16):2198-2210
[40]Burkinshaw BJ,Liang XY,Wong M,et al.A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex[J].Nature Microbiology,2018,3(5):632-640
[41]Wong MJQ,Liang XY,Smart M,et al.Microbial herd protection mediated by antagonistic interaction in polymicrobial communities[J].Applied and Environmental Microbiology,2016,82(23):6881-6888
[42]Si MR,Zhao C,Burkinshaw B,et al.Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(11):E2233-E2242
[43]Wang TT,Si MR,Song YH,et al.Type VI secretion system transports Zn2+to combat multiple stresses and host Immunity[J].PLoS Pathogens,2015,11(7):e1005020
[44]Lin JS,Zhang WP,Cheng JL,et al.A Pseudomonas T6SSeffector recruits PQS-containing outer membrane vesicles for iron acquisition[J].Nature Communications,2017,8:14888
[45]Wan BS,Zhang QF,Ni JJ,et al.Type VI secretion system contributes to enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species(ROS)[J].PLoS Pathogens,2017,13(3):e1006246
[46]Jiang F,Waterfield NR,Yang J,et al.A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells[J].Cell Host&Microbe,2014,15(5):600-610
[47]Li J,Yao YF,Xu HH,et al.SecReT6:a web-based resource for type VI secretion systems found in bacteria[J].Environmental Microbiology,2015,17(7):2196-2202
[48]Lien YW,Lai EM.Type VI secretion effectors:methodologies and biology[J].Frontiers in Cellular and Infection Microbiology,2017,7:254
[2]Aoki SK,Pamma R,Hernday AD,et al.Contact-dependent inhibition of growth in Escherichia coli[J].Science,2005,309(5738):1245-1248
[3]Pukatzki S,Ma AT,Sturtevant D,et al.Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(5):1528-1533
[4]Mougous JD,Cuff ME,Raunser S,et al.A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus[J].Science,2006,312(5779):1526-1530
[5]Ho BT,Dong TG,Mekalanos JJ.A view to a kill:the bacterial type VI secretion system[J].Cell Host&Microbe,2014,15(1):9-21
[6]Basler M.Type VI secretion system:secretion by a contractile nanomachine[J].Philosophical Transactions of the Royal Society of London.Series B,Biological Sciences,2015,370(1679):20150021
[7]Brackmann M,Nazarov S,Wang J,et al.Using force to punch holes:mechanics of contractile nanomachines[J].Trends in Cell Biology,2017,27(9):623-632
[8]Taylor NMI,van Raaij MJ,Leiman PG.Contractile injection systems of bacteriophages and related systems[J].Molecular Microbiology,2018,108(1):6-15
[9]van Son Nguyen,Logger L,Spinelli S,et al.Type VI secretion TssK baseplate protein exhibits structural similarity with phage receptor-binding proteins and evolved to bind the membrane complex[J].Nature Microbiology,2017,2:17103
[10]Leiman PG,Basler M,Ramagopal UA,et al.Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin[J].Proceedings of the National Academy of Sciences of the United States of America,2009,106(11):4154-4159
[11]Shneider MM,Buth SA,Ho BT,et al.PAAR-repeat proteins sharpen and diversify the type VI secretion system spike[J].Nature,2013,500(7462):350-353
[12]Kapitein N,B?nemann G,Pietrosiuk A,et al.ClpV recycles VipA/VipB tubules and prevents non-productive tubule formation to ensure efficient type VI protein secretion[J].Molecular Microbiology,2013,87(5):1013-1028
[13]B?nemann G,Pietrosiuk A,Diemand A,et al.Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion[J].The EMBO Journal,2009,28(4):315-325
[14]Basler M,Mekalanos JJ.Type 6 secretion dynamics within and between bacterial cells[J].Science,2012,337(6096):815
[15]Dong TG,Mekalanos JJ.Characterization of the RpoN regulon reveals differential regulation of T6SS and new flagellar operons in Vibrio cholerae O37 strain V52[J].Nucleic Acids Research,2012,40(16):7766-7775
[16]Zoued A,Durand E,Brunet YR,et al.Priming and polymerization of a bacterial contractile tail structure[J].Nature,2016,531(7592):59-63
[17]Santin YG,Doan T,Lebrun R,et al.In vivo TssA proximity labelling during type VI secretion biogenesis reveals TagA as a protein that stops and holds the sheath[J].Nature Microbiology,2018,3(11):1304-1313
[18]Nazarov S,Schneider JP,Brackmann M,et al.Cryo-EMreconstruction of Type VI secretion system baseplate and sheath distal end[J].The EMBO Journal,2018,37(4):e97103
[19]Wang J,Brackmann M,Casta?o-Díez D,et al.Cryo-EM structure of the extended type VI secretion system sheath-tube complex[J].Nature Microbiology,2017,2(11):1507-1512
[20]Hood RD,Singh P,Hsu F,et al.A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria[J].Cell Host&Microbe,2010,7(1):25-37
[21]Dong TG,Dong S,Catalano C,et al.Generation of reactive oxygen species by lethal attacks from competing microbes[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(7):2181-2186
[22]Russell AB,Peterson SB,Mougous JD.Type VI secretion system effectors:poisons with a purpose[J].Nature Reviews Microbiology,2014,12(2):137-148
[23]Pukatzki S,Ma AT,Revel AT,et al.Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(39):15508-15513
[24]Dong TG,Ho BT,Yoder-Himes DR,et al.Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(7):2623-2628
[25]Zheng J,Ho B,Mekalanos JJ.Genetic analysis of anti-amoebae and anti-bacterial activities of the type VI secretion system in Vibrio cholerae[J].PLoS One,2011,6(8):e23876
[26]Ma JL,Pan ZH,Huang JH,et al.The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems[J].Virulence,2017,8(7):1189-1202
[27]Filloux A,Hachani A,Bleves S.The bacterial type VI secretion machine:yet another player for protein transport across membranes[J].Microbiology,2008,154:1570-1583
[28]Pukatzki S,McAuley SB,Miyata ST.The type VI secretion system:translocation of effectors and effector-domains[J].Current Opinion in Microbiology,2009,12(1):11-17
[29]Ma AT,McAuley S,Pukatzki S,et al.Translocation of a Vibrio cholerae type VI secretion effector requires bacterial endocytosis by host cells[J].Cell Host&Microbe,2009,5(3):234-243
[30]Zheng J,Leung KY.Dissection of a type VI secretion system in Edwardsiella tarda[J].Molecular Microbiology,2007,66(5):1192-1206
[31]Silverman JM,Agnello DM,Zheng HJ,et al.Haemolysin coregulated protein is an exported receptor and chaperone of Type VI secretion substrates[J].Molecular Cell,2013,51(5):584-593
[32]Russell AB,Singh P,Brittnacher M,et al.A widespread bacterial type VI secretion effector superfamily identified using a heuristic approach[J].Cell Host&Microbe,2012,11(5):538-549
[33]Mac Intyre DL,Miyata ST,Kitaoka M,et al.The Vibrio cholerae type VI secretion system displays antimicrobial properties[J].Proceedings of the National Academy of Sciences of the United States of America,2010,107(45):19520-19524
[34]Li M,Le Trong I,Carl MA,et al.Structural basis for type VIsecretion effector recognition by a cognate immunity protein[J].PLoS Pathogens,2012,8(4):e1002613
[35]Liang XY,Moore R,Wilton M,et al.Identification of divergent type VI secretion effectors using a conserved chaperone domain[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(29):9106-9111
[36]Hachani A,Allsopp LP,Oduko Y,et al.The VgrG proteins are“àla carte”delivery systems for bacterial type VI effectors[J].The Journal of Biological Chemistry,2014,289(25):17872-17884
[37]Bondage DD,Lin JS,Ma LS,et al.VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor-effector complex[J].Proceedings of the National Academy of Sciences of the United States of America,2016,113(27):E3931-E3940
[38]Flaugnatti N,Le TTH,Canaan S,et al.A phospholipase A1antibacterial Type VI secretion effector interacts directly with the C-terminal domain of the VgrG spike protein for delivery[J].Molecular Microbiology,2016,99(6):1099-1118
[39]Unterweger D,Kostiuk B,?tjengerdes R,et al.Chimeric adaptor proteins translocate diverse type VI secretion system effectors in Vibrio cholerae[J].The EMBO Journal,2015,34(16):2198-2210
[40]Burkinshaw BJ,Liang XY,Wong M,et al.A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex[J].Nature Microbiology,2018,3(5):632-640
[41]Wong MJQ,Liang XY,Smart M,et al.Microbial herd protection mediated by antagonistic interaction in polymicrobial communities[J].Applied and Environmental Microbiology,2016,82(23):6881-6888
[42]Si MR,Zhao C,Burkinshaw B,et al.Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis[J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(11):E2233-E2242
[43]Wang TT,Si MR,Song YH,et al.Type VI secretion system transports Zn2+to combat multiple stresses and host Immunity[J].PLoS Pathogens,2015,11(7):e1005020
[44]Lin JS,Zhang WP,Cheng JL,et al.A Pseudomonas T6SSeffector recruits PQS-containing outer membrane vesicles for iron acquisition[J].Nature Communications,2017,8:14888
[45]Wan BS,Zhang QF,Ni JJ,et al.Type VI secretion system contributes to enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species(ROS)[J].PLoS Pathogens,2017,13(3):e1006246
[46]Jiang F,Waterfield NR,Yang J,et al.A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells[J].Cell Host&Microbe,2014,15(5):600-610
[47]Li J,Yao YF,Xu HH,et al.SecReT6:a web-based resource for type VI secretion systems found in bacteria[J].Environmental Microbiology,2015,17(7):2196-2202
[48]Lien YW,Lai EM.Type VI secretion effectors:methodologies and biology[J].Frontiers in Cellular and Infection Microbiology,2017,7:254