Advertisement

Biological Diversity and Evolution of Type IV Secretion Systems

  • Peter J. Christie
  • Laura Gomez Valero
  • Carmen Buchrieser
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 413)

Abstract

The bacterial type IV secretion systems (T4SSs) are a highly functionally and structurally diverse superfamily of secretion systems found in many species of Gram-negative and -positive bacteria. Collectively, the T4SSs can translocate DNA and monomeric and multimeric protein substrates to a variety of bacterial and eukaryotic cell types. Detailed phylogenomics analyses have established that the T4SSs evolved from ancient conjugation machines whose original functions were to disseminate mobile DNA elements within and between bacterial species. How members of the T4SS superfamily evolved to recognize and translocate specific substrate repertoires to prokaryotic or eukaryotic target cells is a fascinating question from evolutionary, biological, and structural perspectives. In this chapter, we will summarize recent findings that have shaped our current view of the biological diversity of the T4SSs. We focus mainly on two subtypes, designated as the types IVA (T4ASS) and IVB (T4BSS) systems that respectively are represented by the paradigmatic Agrobacterium tumefaciens VirB/VirD4 and Legionella pneumophila Dot/Icm T4SSs. We present current information about the composition and architectures of these representative systems. We also describe how these and a few related T4ASS and T4BSS members evolved as specialized nanomachines through acquisition of novel domains or subunits, a process that ultimately generated extensive genetic and structural mosaicism among this secretion superfamily. Finally, we present new phylogenomics information establishing that the T4BSSs are much more broadly distributed than initially envisioned.

Keywords

Type IV secretion Conjugation DNA transfer Pathogenesis Effector translocation Legionella Dot/Icm Coupling protein Traffic ATPases 

Notes

Acknowledgements

Work in the Christie laboratory was supported by NIH grants R01GM48476 and R21AI105454. Work in the CB laboratory is financed by the Institut Pasteur, the grants N°ANR-10-LABX-62-IBEID, the Fondation pour la Recherche Médicale (FRM) grant N° DEQ 20120323697, and the Infect-ERA project EUGENPATH (ANR-13-IFEC-0003-02).

References

  1. Alvarez-Martinez CE, Christie PJ (2009) Biological diversity of prokaryotic type IV secretion systems. Microbiol Mol Biol Rev 73:775–808CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aly KA, Baron C (2007) The VirB5 protein localizes to the T-pilus tips in Agrobacterium tumefaciens. Microbiology 153:3766–3775CrossRefPubMedGoogle Scholar
  3. Andrews HL, Vogel JP, Isberg RR (1998) Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect Immun 66:950–958PubMedPubMedCentralGoogle Scholar
  4. Anthony KG, Klimke WA, Manchak J, Frost LA (1999) Comparison of proteins involved in pilus synthesis and mating pair stabilization from the related plasmids F and R100-1: insights into the mechanism of conjugation. J Bacteriol 181:5149–5159PubMedPubMedCentralGoogle Scholar
  5. Aras RA, Fischer W, Perez-Perez GI, Crosatti M, Ando T, Haas R, Blaser MJ (2003) Plasticity of repetitive DNA sequences within a bacterial (Type IV) secretion system component. J Exp Med 198:1349–1360.  https://doi.org/10.1084/jem.20030381CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arutyunov D, Frost LS (2013) F conjugation: back to the beginning. Plasmid 70:18–32.  https://doi.org/10.1016/j.plasmid.2013.03.010CrossRefPubMedGoogle Scholar
  7. Asrat S, Davis KM, Isberg RR (2015) Modulation of the host innate immune and inflammatory response by translocated bacterial proteins. Cell Microbiol 17:785–795.  https://doi.org/10.1111/cmi.12445CrossRefPubMedPubMedCentralGoogle Scholar
  8. Atmakuri K, Ding Z, Christie PJ (2003) VirE2, a type IV secretion substrate, interacts with the VirD4 transfer protein at cell poles of Agrobacterium tumefaciens. Mol Microbiol 49:1699–1713CrossRefPubMedPubMedCentralGoogle Scholar
  9. Atmakuri K, Cascales E, Christie PJ (2004) Energetic components VirD4, VirB11 and VirB4 mediate early DNA transfer reactions required for bacterial type IV secretion. Mol Microbiol 54:1199–1211CrossRefPubMedGoogle Scholar
  10. Audette GF, Manchak J, Beatty P, Klimke WA, Frost LS (2007) Entry exclusion in F-like plasmids requires intact TraG in the donor that recognizes its cognate TraS in the recipient. Microbiology 153:442–451CrossRefPubMedGoogle Scholar
  11. Backert S, Meyer TF (2006) Type IV secretion systems and their effectors in bacterial pathogenesis. Curr Opin Microbiol 9(2):207–217.  https://doi.org/10.1016/j.mib.2006.02.008CrossRefPubMedGoogle Scholar
  12. Backert S, Tegtmeyer N (2017) Type IV secretion and signal transduction of Helicobacter pylori CagA through interactions with host cell receptors. Toxins (Basel) 9.  https://doi.org/10.3390/toxins9040115
  13. Backert S, Tegtmeyer N, Fischer W (2015) Composition, structure and function of the Helicobacter pylori cag pathogenicity island encoded type IV secretion system. Future Microbiol 10(6):955–965.  https://doi.org/10.2217/fmb.15.32CrossRefPubMedPubMedCentralGoogle Scholar
  14. Barrozo RM et al (2013) Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathog 9:e1003189.  https://doi.org/10.1371/journal.ppat.1003189CrossRefPubMedPubMedCentralGoogle Scholar
  15. Beare PA, Howe D, Cockrell DC, Omsland A, Hansen B, Heinzen RA (2009) Characterization of a Coxiella burnetii ftsZ mutant generated by Himar1 transposon mutagenesis. J Bacteriol 191:1369–1381CrossRefPubMedGoogle Scholar
  16. Beranek A, Zettl M, Lorenzoni K, Schauer A, Manhart M, Koraimann G (2004) Thirty-eight C-terminal amino acids of the coupling protein TraD of the F-like conjugative resistance plasmid R1 are required and sufficient to confer binding to the substrate selector protein TraM. J Bacteriol 186:6999–7006CrossRefPubMedPubMedCentralGoogle Scholar
  17. Berger BR, Christie PJ (1994) Genetic complementation analysis of the Agrobacterium tumefaciens virB operon: virB2 through virB11 are essential virulence genes. J Bacteriol 176:3646–3660CrossRefPubMedPubMedCentralGoogle Scholar
  18. Berger KH, Isberg RR (1993) Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol 7:7–19CrossRefPubMedGoogle Scholar
  19. Berger KH, Merriam JJ, Isberg RR (1994) Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol Microbiol 14:809–822CrossRefPubMedGoogle Scholar
  20. Bhatty M, Laverde Gomez JA, Christie PJ (2013) The expanding bacterial type IV secretion lexicon. Res Microbiol 164:620–639.  https://doi.org/10.1016/j.resmic.2013.03.012CrossRefPubMedGoogle Scholar
  21. Bingle LE, Bailey CM, Pallen MJ (2008) Type VI secretion: a beginner’s guide. Curr Opin Microbiol 11:3–8.  https://doi.org/10.1016/j.mib.2008.01.006CrossRefPubMedGoogle Scholar
  22. Bradley DE (1980) Morphological and serological relationships of conjugative pili. Plasmid 4:155–169CrossRefPubMedGoogle Scholar
  23. Bradley DE, Taylor DE, Cohen DR (1980) Specification of surface mating systems among conjugative drug resistance plasmids in Escherichia coli K-12. J Bacteriol 143:1466–1470PubMedPubMedCentralGoogle Scholar
  24. Brand BC, Sadosky AB, Shuman HA (1994) The Legionella pneumophila icm locus: a set of genes required for intracellular multiplication in human macrophages. Mol Microbiol 14:797–808CrossRefPubMedGoogle Scholar
  25. Burstein D et al (2016) Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires. Nat Genet 48:167–175.  https://doi.org/10.1038/ng.3481CrossRefPubMedPubMedCentralGoogle Scholar
  26. Buscher BA, Conover GM, Miller JL, Vogel SA, Meyers SN, Isberg RR, Vogel JP (2005) The DotL protein, a member of the TraG-coupling protein family, is essential for viability of Legionella pneumophila strain Lp02. J Bacteriol 187:2927–2938.  https://doi.org/10.1128/JB.187.9.2927-2938.2005CrossRefPubMedPubMedCentralGoogle Scholar
  27. Cabezon E, Sastre JI, de la Cruz F (1997) Genetic evidence of a coupling role for the TraG protein family in bacterial conjugation. Mol Gen Genet 254:400–406CrossRefPubMedGoogle Scholar
  28. Cabezon E, Ripoll-Rozada J, Pena A, de la Cruz F, Arechaga I (2014) Towards an integrated model of bacterial conjugation. FEMS Microbiol Rev 39:81–95.  https://doi.org/10.1111/1574-6976.12085CrossRefPubMedGoogle Scholar
  29. Carey KL, Newton HJ, Luhrmann A, Roy CR (2011) The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication. PLoS Path 7:e1002056.  https://doi.org/10.1371/journal.ppat.1002056CrossRefGoogle Scholar
  30. Cascales E (2008) The type VI secretion toolkit. EMBO Rep 9:735–741.  https://doi.org/10.1038/embor.2008.131CrossRefPubMedPubMedCentralGoogle Scholar
  31. Cascales E, Christie PJ (2003) The versatile bacterial type IV secretion systems. Nat Rev Microbiol 1:137–150CrossRefPubMedGoogle Scholar
  32. Cascales E, Christie PJ (2004) Definition of a bacterial type IV secretion pathway for a DNA substrate. Science 304:1170–1173CrossRefPubMedGoogle Scholar
  33. Cazalet C, Gomez-Valero L, Rusniok C, Lomma M, Dervins-Ravault D, Newton HJ, Sansom FM, Jarraud S, Zidane N, Ma L, Bouchier C, Etienne J, Hartland EL, Buchrieser C (2010) Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires’ disease. PLoS Genet 19, 6(2):e1000851.  https://doi.org/10.1371/journal.pgen.1000851CrossRefPubMedPubMedCentralGoogle Scholar
  34. Cazalet C et al (2004) Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat Genet 36:1165–1173.  https://doi.org/10.1038/ng1447 (doi:ng1447 [pii])
  35. Chandran Darbari V, Waksman G (2015) Structural biology of bacterial type IV secretion systems. Annu Rev Biochem 84:603–629.  https://doi.org/10.1146/annurev-biochem-062911-102821CrossRefPubMedGoogle Scholar
  36. Chen C et al (2010) Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii. Proc Natl Acad Sci U S A 107:21755–21760.  https://doi.org/10.1073/pnas.1010485107CrossRefPubMedPubMedCentralGoogle Scholar
  37. Christie PJ, Vogel JP (2000) Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends Microbiol 8:354–360CrossRefPubMedPubMedCentralGoogle Scholar
  38. Christie PJ, Atmakuri K, Krishnamoorthy V, Jakubowski S, Cascales E (2005) Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu Rev Microbiol 59:451–485CrossRefPubMedGoogle Scholar
  39. Clarke M, Maddera L, Harris RL, Silverman PM (2008) F-pili dynamics by live-cell imaging. Proc Natl Acad Sci U S A 105:17978–17981CrossRefPubMedPubMedCentralGoogle Scholar
  40. Coers J, Kagan JC, Matthews M, Nagai H, Zuckman DM, Roy CR (2000) Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Mol Microbiol 38:719–736CrossRefPubMedGoogle Scholar
  41. Conradi J, Huber S, Gaus K, Mertink F, Royo GS, Strijowski U, Backert S, Sewald N (2012) Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins alphaVbeta3 and alpha5beta1. Amino Acids 43(1):219–232.  https://doi.org/10.1007/s00726-011-1066-0CrossRefPubMedGoogle Scholar
  42. Costa J, Tiago I, Da Costa MS, Verissimo A (2010) Molecular evolution of Legionella pneumophila dotA gene, the contribution of natural environmental strains. Environ Microbiol 12:2711–2729.  https://doi.org/10.1111/j.1462-2920.2010.02240.xCrossRefPubMedGoogle Scholar
  43. de Felipe KS, Pampou S, Jovanovic OS, Pericone CD, Ye SF, Kalachikov S, Shuman HA (2005) Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J Bacteriol 187:7716–7726.  https://doi.org/10.1128/jb.187.22.7716-7726.2005 (doi:187/22/7716 [pii])
  44. de Paz HD, Larrea D, Zunzunegui S, Dehio C, de la Cruz F, Llosa M (2010) Functional dissection of the conjugative coupling protein TrwB. J Bacteriol 192:2655–2669.  https://doi.org/10.1128/JB.01692-09CrossRefPubMedPubMedCentralGoogle Scholar
  45. Dehio C (2008) Infection-associated type IV secretion systems of Bartonella and their diverse roles in host cell interaction. Cell Microbiol 10:1591–1598CrossRefPubMedPubMedCentralGoogle Scholar
  46. Ding H et al (2012) Helicobacter pylori chaperone-like protein CagT plays an essential role in the translocation of CagA into host cells. J Microbiol Biotechnol 22:1343–1349CrossRefPubMedGoogle Scholar
  47. Dumenil G, Isberg RR (2001) The Legionella pneumophila IcmR protein exhibits chaperone activity for IcmQ by preventing its participation in high-molecular-weight complexes. Mol Microbiol 40:1113–1127CrossRefPubMedGoogle Scholar
  48. Edelstein PH, Edelstein MA, Higa F, Falkow S (1999) Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model. Proc Natl Acad Sci U S A 96:8190–8195CrossRefPubMedPubMedCentralGoogle Scholar
  49. Eicher SC, Dehio C (2012) Bartonella entry mechanisms into mammalian host cells. Cell Microbiol 14:1166–1173.  https://doi.org/10.1111/j.1462-5822.2012.01806.xCrossRefPubMedGoogle Scholar
  50. Escoll P, Mondino S, Rolando M, Buchrieser C (2016) Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy. Nat Rev Microbiol 14:5–19.  https://doi.org/10.1038/nrmicro.2015.1CrossRefPubMedGoogle Scholar
  51. Farelli JD et al (2013) IcmQ in the Type 4b secretion system contains an NAD+ binding domain. Structure 21:1361–1373.  https://doi.org/10.1016/j.str.2013.05.017CrossRefPubMedGoogle Scholar
  52. Feldman M, Segal G (2004) A specific genomic location within the icm/dot pathogenesis region of different Legionella species encodes functionally similar but nonhomologous virulence proteins. Infect Immun 72:4503–4511.  https://doi.org/10.1128/IAI.72.8.4503-4511.2004CrossRefPubMedPubMedCentralGoogle Scholar
  53. Feldman M, Zusman T, Hagag S, Segal G (2005) Coevolution between nonhomologous but functionally similar proteins and their conserved partners in the Legionella pathogenesis system. Proc Natl Acad Sci U S A 102:12206–12211.  https://doi.org/10.1073/pnas.0501850102CrossRefPubMedPubMedCentralGoogle Scholar
  54. Fernandez D, Spudich GM, Zhou XR, Christie PJ (1996) The Agrobacterium tumefaciens VirB7 lipoprotein is required for stabilization of VirB proteins during assembly of the T-complex transport apparatus. J Bacteriol 178:3168–3176CrossRefPubMedPubMedCentralGoogle Scholar
  55. Finsel I, Hilbi H (2015) Formation of a pathogen vacuole according to Legionella pneumophila: how to kill one bird with many stones. Cell Microbiol 17:935–950.  https://doi.org/10.1111/cmi.12450CrossRefPubMedGoogle Scholar
  56. Firth N, Skurray R (1992) Characterization of the F plasmid bifunctional conjugation gene, traG. Mol Gen Genet 232:145–153CrossRefPubMedGoogle Scholar
  57. Fischer W (2011) Assembly and molecular mode of action of the Helicobacter pylori Cag type IV secretion apparatus. FEBS J 278:1203–1212.  https://doi.org/10.1111/j.1742-4658.2011.08036.xCrossRefPubMedGoogle Scholar
  58. Frick-Cheng AE, Pyburn TM, Voss BJ, McDonald WH, Ohi MD, Cover TL (2016) Molecular and structural analysis of the Helicobacter pylori cag type IV secretion system core complex. MBio 7:e02001–e02015.  https://doi.org/10.1128/mBio.02001-15CrossRefPubMedPubMedCentralGoogle Scholar
  59. Fronzes R, Schafer E, Wang L, Saibil HR, Orlova EV, Waksman G (2009) Structure of a type IV secretion system core complex. Science 323:266–268CrossRefPubMedGoogle Scholar
  60. Fullner KJ, Lara JC, Nester EW (1996) Pilus assembly by Agrobacterium T-DNA transfer genes. Science 273:1107–1109CrossRefPubMedGoogle Scholar
  61. Garcillan-Barcia MP, de la Cruz F (2008) Why is entry exclusion an essential feature of conjugative plasmids? Plasmid 60:1–18.  https://doi.org/10.1016/j.plasmid.2008.03.002CrossRefPubMedGoogle Scholar
  62. Ghosal D, Chang YW, Jeong KC, Vogel JP, Jensen GJ (2017) In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography. EMBO Rep 18:726–732.  https://doi.org/10.15252/embr.201643598CrossRefPubMedPubMedCentralGoogle Scholar
  63. Gillespie JJ et al (2009) An anomalous type IV secretion system in Rickettsia is evolutionarily conserved. PLoS ONE 4:e4833CrossRefPubMedPubMedCentralGoogle Scholar
  64. Gillespie JJ, Brayton KA, Williams KP, Diaz MA, Brown WC, Azad AF, Sobral BW (2010) Phylogenomics reveals a diverse Rickettsiales type IV secretion system. Infect Immun 78:1809–1823.  https://doi.org/10.1128/IAI.01384-09CrossRefPubMedPubMedCentralGoogle Scholar
  65. Gomez FA, Tobar JA, Henriquez V, Sola M, Altamirano C, Marshall SH (2013) Evidence of the presence of a functional Dot/Icm type IV-B secretion system in the fish bacterial pathogen Piscirickettsia salmonis. PLoS ONE 8:e54934.  https://doi.org/10.1371/journal.pone.0054934CrossRefPubMedPubMedCentralGoogle Scholar
  66. Gomez-Valero L, Buchrieser C (2013) Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication. Cold Spring Harb Perspect Med 3  https://doi.org/10.1101/cshperspect.a009993CrossRefPubMedPubMedCentralGoogle Scholar
  67. Gomez-Valero L, Rusniok C, Cazalet C, Buchrieser C (2011) Comparative and functional genomics of legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol 2:208.  https://doi.org/10.3389/fmicb.2011.00208CrossRefPubMedPubMedCentralGoogle Scholar
  68. Gomez-Valero L et al (2014) Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires’ disease. Genome Biol 15:505.  https://doi.org/10.1186/PREACCEPT-1086350395137407CrossRefPubMedPubMedCentralGoogle Scholar
  69. Gomis-Ruth FX, Moncalian G, Perez-Luque R, Gonzalez A, Cabezon E, de la Cruz F, Coll M (2001) The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase. Nature 409:637–641CrossRefPubMedGoogle Scholar
  70. Gomis-Ruth FX, Sola M, de la Cruz F, Coll M (2004) Coupling factors in macromolecular type-IV secretion machineries. Curr Pharm Des 10:1551–1565CrossRefPubMedGoogle Scholar
  71. Gordon JE et al (2017) Use of chimeric type IV secretion systems to define contributions of outer membrane subassemblies for contact-dependent translocation. Mol Microbiol 105:273–293.  https://doi.org/10.1111/mmi.13700CrossRefPubMedPubMedCentralGoogle Scholar
  72. Grohmann E, Christie PJ, Waksman G, Backert S (2018) Type IV secretion in gram-negative and gram-positive bacteria. Mol Microbiol 107:455–471  https://doi.org/10.1111/mmi.13896CrossRefPubMedPubMedCentralGoogle Scholar
  73. Guglielmini J, de la Cruz F, Rocha EP (2013) Evolution of conjugation and type IV secretion systems. Mol Biol Evol 30:315–331.  https://doi.org/10.1093/molbev/mss221CrossRefPubMedGoogle Scholar
  74. Gyohda A, Komano T (2000) Purification and characterization of the R64 shufflon-specific recombinase. J Bacteriol 182:2787–2792CrossRefPubMedPubMedCentralGoogle Scholar
  75. Hubber A, Roy CR (2010) Modulation of host cell function by Legionella pneumophila type IV effectors. Annu Rev Cell Dev Biol 26:261–283.  https://doi.org/10.1146/annurev-cellbio-100109-104034CrossRefPubMedGoogle Scholar
  76. Jakubowski SJ, Krishnamoorthy V, Christie PJ (2003) Agrobacterium tumefaciens VirB6 protein participates in formation of VirB7 and VirB9 complexes required for type IV secretion. J Bacteriol 185:2867–2878CrossRefPubMedPubMedCentralGoogle Scholar
  77. Jakubowski SJ, Cascales E, Krishnamoorthy V, Christie PJ (2005) Agrobacterium tumefaciens VirB9, an outer-membrane-associated component of a type IV secretion system, regulates substrate selection and T-pilus biogenesis. J Bacteriol 187:3486–3495CrossRefPubMedPubMedCentralGoogle Scholar
  78. Jeong KC, Ghosal D, Chang YW, Jensen GJ, Vogel JP (2017) Polar delivery of Legionella type IV secretion system substrates is essential for virulence. Proc Natl Acad Sci U S A 114:8077–8082.  https://doi.org/10.1073/pnas.1621438114CrossRefPubMedPubMedCentralGoogle Scholar
  79. Johnson EM, Gaddy JA, Voss BJ, Hennig EE, Cover TL (2014) Genes required for assembly of pili associated with the Helicobacter pylori cag type IV secretion system. Infect Immun 82:3457–3470.  https://doi.org/10.1128/IAI.01640-14CrossRefPubMedPubMedCentralGoogle Scholar
  80. Klimke WA, Rypien CD, Klinger B, Kennedy RA, Rodriguez-Maillard JM, Frost LS (2005) The mating pair stabilization protein, TraN, of the F plasmid is an outer-membrane protein with two regions that are important for its function in conjugation. Microbiology 151:3527–3540.  https://doi.org/10.1099/mic.0.28025-0CrossRefPubMedGoogle Scholar
  81. Ko KS, Hong SK, Lee HK, Park MY, Kook YH (2003) Molecular evolution of the dotA gene in Legionella pneumophila. J Bacteriol 185:6269–6277CrossRefPubMedPubMedCentralGoogle Scholar
  82. Komano T, Yoshida T, Narahara K, Furuya N (2000) The transfer region of IncI1 plasmid R64: similarities between R64 tra and Legionella icm/dot genes. Mol Microbiol 35:1348–1359CrossRefPubMedGoogle Scholar
  83. Kubori T, Nagai H (2015) The Type IVB secretion system: an enigmatic chimera. Curr Opin Microbiol 29:22–29.  https://doi.org/10.1016/j.mib.2015.10.001CrossRefPubMedGoogle Scholar
  84. Kubori T, Koike M, Bui XT, Higaki S, Aizawa S, Nagai H (2014) Native structure of a type IV secretion system core complex essential for Legionella pathogenesis. Proc Natl Acad Sci U S A 111:11804–11809.  https://doi.org/10.1073/pnas.1404506111CrossRefPubMedPubMedCentralGoogle Scholar
  85. Kwak MJ et al (2017) Architecture of the type IV coupling protein complex of Legionella pneumophila. Nat Microbiol 2:17114.  https://doi.org/10.1038/nmicrobiol.2017.114CrossRefPubMedGoogle Scholar
  86. Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, König W, Backert S (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449(7164):862–866.  https://doi.org/10.1038/nature06187CrossRefPubMedGoogle Scholar
  87. Labra A, Arredondo-Zelada O, Flores-Herrera P, Marshall SH, Gomez FA (2016) In silico identification and characterization of putative Dot/Icm secreted virulence effectors in the fish pathogen Piscirickettsia salmonis. Microb Pathog 92:11–18.  https://doi.org/10.1016/j.micpath.2015.12.002CrossRefPubMedGoogle Scholar
  88. Larson CL, Martinez E, Beare PA, Jeffrey B, Heinzen RA, Bonazzi M (2016) Right on Q: genetics begin to unravel Coxiella burnetii host cell interactions. Future Microbiol 11:919–939.  https://doi.org/10.2217/fmb-2016-0044CrossRefPubMedPubMedCentralGoogle Scholar
  89. Lawley TD, Klimke WA, Gubbins MJ, Frost LS (2003) F factor conjugation is a true type IV secretion system. FEMS Microbiol Lett 224:1–15CrossRefPubMedGoogle Scholar
  90. Leclerque A, Kleespies RG (2008) Type IV secretion system components as phylogenetic markers of entomopathogenic bacteria of the genus Rickettsiella. FEMS Microbiol Lett 279:167–173.  https://doi.org/10.1111/j.1574-6968.2007.01025.xCrossRefPubMedGoogle Scholar
  91. Li F, Alvarez-Martinez C, Chen Y, Choi KJ, Yeo HJ, Christie PJ (2012) Enterococcus faecalis PrgJ, a VirB4-like ATPase, mediates pCF10 conjugative transfer through substrate binding. J Bacteriol 194:404140–404151.  https://doi.org/10.1128/JB.00648-12CrossRefGoogle Scholar
  92. Lifshitz Z et al (2013) Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal. Proc Natl Acad Sci U S A 110:E707–E715.  https://doi.org/10.1073/pnas.1215278110CrossRefPubMedPubMedCentralGoogle Scholar
  93. Locht C, Coutte L, Mielcarek N (2011) The ins and outs of pertussis toxin. FEBS J 278(23):4668–4682.  https://doi.org/10.1111/j.1742-4658.2011.08237.xCrossRefPubMedGoogle Scholar
  94. Low HH et al (2014) Structure of a type IV secretion system. Nature 508:550–553.  https://doi.org/10.1038/nature13081CrossRefPubMedPubMedCentralGoogle Scholar
  95. Lu J, Frost LS (2005) Mutations in the C-terminal region of TraM provide evidence for in vivo TraM-TraD interactions during F-plasmid conjugation. J Bacteriol 187:4767–4773CrossRefPubMedPubMedCentralGoogle Scholar
  96. Lu J, Wong JJ, Edwards RA, Manchak J, Frost LS, Glover JN (2008) Structural basis of specific TraD-TraM recognition during F plasmid-mediated bacterial conjugation. Mol Microbiol 70:89–99CrossRefPubMedGoogle Scholar
  97. Luo ZQ, Isberg RR (2004) Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc Natl Acad Sci U S A 101:841–846CrossRefPubMedPubMedCentralGoogle Scholar
  98. Lurie-Weinberger MN, Gomez-Valero L, Merault N, Glockner G, Buchrieser C, Gophna U (2010) The origins of eukaryotic-like proteins in Legionella pneumophila. Int J Med Microbiol 300:470–481.  https://doi.org/10.1016/j.ijmm.2010.04.016CrossRefPubMedGoogle Scholar
  99. Marra A, Blander SJ, Horwitz MA, Shuman HA (1992) Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc Natl Acad Sci U S A 89:9607–9611CrossRefPubMedPubMedCentralGoogle Scholar
  100. Marrero J, Waldor MK (2007) Determinants of entry exclusion within Eex and TraG are cytoplasmic. J Bacteriol 189:6469–6473CrossRefPubMedPubMedCentralGoogle Scholar
  101. Matthews M, Roy CR (2000) Identification and subcellular localization of the Legionella pneumophila IcmX protein: a factor essential for establishment of a replicative organelle in eukaryotic host cells. Infect Immun 68:3971–3982CrossRefPubMedPubMedCentralGoogle Scholar
  102. Mauel MJ, Giovannoni SJ, Fryer JL (1999) Phylogenetic analysis of Piscirickettsia salmonis by 16S, internal transcribed spacer (ITS) and 23S ribosomal DNA sequencing. Dis Aquat Organ 35:115–123.  https://doi.org/10.3354/dao035115CrossRefPubMedGoogle Scholar
  103. Middleton R, Sjolander K, Krishnamurthy N, Foley J, Zambryski P (2005) Predicted hexameric structure of the Agrobacterium VirB4 C terminus suggests VirB4 acts as a docking site during type IV secretion. Proc Natl Acad Sci U S A 102:1685–1690.  https://doi.org/10.1073/pnas.0409399102CrossRefPubMedPubMedCentralGoogle Scholar
  104. Moffatt JH, Newton P, Newton HJ (2015) Coxiella burnetii: turning hostility into a home. Cell Microbiol 17:621–631.  https://doi.org/10.1111/cmi.12432CrossRefPubMedGoogle Scholar
  105. Nagai H, Kubori T (2011) Type IVB secretion systems of Legionella and other Gram-negative bacteria. Front Microbiol 2:136.  https://doi.org/10.3389/fmicb.2011.00136CrossRefPubMedPubMedCentralGoogle Scholar
  106. Nagai H, Roy CR (2001) The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter. EMBO J 20:5962–5970CrossRefPubMedPubMedCentralGoogle Scholar
  107. Nagai H, Kagan JC, Zhu X, Kahn RA, Roy CR (2002) A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295:679–682CrossRefPubMedGoogle Scholar
  108. Nakano N, Kubori T, Kinoshita M, Imada K, Nagai H (2010) Crystal structure of Legionella DotD: insights into the relationship between type IVB and type II/III secretion systems. PLoS Pathog 6:e1001129.  https://doi.org/10.1371/journal.ppat.1001129CrossRefPubMedPubMedCentralGoogle Scholar
  109. Ninio S, Zuckman-Cholon DM, Cambronne ED, Roy CR (2005) The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation. Mol Microbiol 55:912–926CrossRefPubMedGoogle Scholar
  110. Noto JM, Lee JY, Gaddy JA, Cover TL, Amieva MR, Peek RM Jr (2015) Regulation of Helicobacter pylori virulence within the context of iron deficiency. J Infect Dis 211:1790–1794.  https://doi.org/10.1093/infdis/jiu805CrossRefPubMedGoogle Scholar
  111. O’Connor TJ, Boyd D, Dorer MS, Isberg RR (2012) Aggravating genetic interactions allow a solution to redundancy in a bacterial pathogen. Science 338:1440–1444.  https://doi.org/10.1126/science.1229556CrossRefPubMedPubMedCentralGoogle Scholar
  112. Paranchych W, Frost LS (1988) The physiology and biochemistry of pili. Adv Microb Physiol 29:53–114CrossRefPubMedGoogle Scholar
  113. Pena A et al (2012) The sexameric structure of a conjugative VirB4 protein ATPase provides new insights for a functional and phylogenetic relationship with DNA translocases. J Biol Chem 287:39925–39932.  https://doi.org/10.1074/jbc.M112.413849CrossRefPubMedPubMedCentralGoogle Scholar
  114. Purcell MW, Shuman HA (1998) The Legionella pneumophila icmGCDJBF genes are required for killing of human macrophages. Infect Immun 66:2245–2255PubMedPubMedCentralGoogle Scholar
  115. Qiu J, Luo ZQ (2017) Legionella and Coxiella effectors: strength in diversity and activity. Nat Rev Microbiol 15:591–605.  https://doi.org/10.1038/nrmicro.2017.67CrossRefPubMedGoogle Scholar
  116. Ramsey ME, Woodhams KL, Dillard JP (2011) The gonococcal genetic island and type IV secretion in the pathogenic Neisseria. Front Microbiol 2:61.  https://doi.org/10.3389/fmicb.2011.00061CrossRefPubMedPubMedCentralGoogle Scholar
  117. Rances E, Voronin D, Tran-Van V, Mavingui P (2008) Genetic and functional characterization of the type IV secretion system in Wolbachia. J Bacteriol 190:5020–5030CrossRefPubMedPubMedCentralGoogle Scholar
  118. Raychaudhury S et al (2009) Structure and function of interacting IcmR-IcmQ domains from a type IVb secretion system in Legionella pneumophila. Structure 17:590–601.  https://doi.org/10.1016/j.str.2009.02.011CrossRefPubMedPubMedCentralGoogle Scholar
  119. Ripoll-Rozada J, Zunzunegui S, de la Cruz F, Arechaga I, Cabezon E (2013) Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular motors in type IV secretion systems. J Bacteriol 195:4195–4201.  https://doi.org/10.1128/JB.00437-13CrossRefPubMedPubMedCentralGoogle Scholar
  120. Rohde M, Puls J, Buhrdorf R, Fischer W, Haas R (2003) A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system. Mol Microbiol 49:219–234CrossRefPubMedGoogle Scholar
  121. Roy CR, Isberg RR (1997) Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages. Infect Immun 65:571–578PubMedPubMedCentralGoogle Scholar
  122. Sadosky AB, Wiater LA, Shuman HA (1993) Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infect Immun 61:5361–5373PubMedPubMedCentralGoogle Scholar
  123. Sagulenko E, Sagulenko V, Chen J, Christie PJ (2001) Role of Agrobacterium VirB11 ATPase in T-pilus assembly and substrate selection. J Bacteriol 183:5813–5825.  https://doi.org/10.1128/JB.183.20.5813-5825.2001CrossRefPubMedPubMedCentralGoogle Scholar
  124. Sampei G, Furuya N, Tachibana K, Saitou Y, Suzuki T, Mizobuchi K, Komano T (2010) Complete genome sequence of the incompatibility group I1 plasmid R64. Plasmid 64:92–103.  https://doi.org/10.1016/j.plasmid.2010.05.005CrossRefPubMedGoogle Scholar
  125. Sastre JI, Cabezon E, de la Cruz F (1998) The carboxyl terminus of protein TraD adds specificity and efficiency to F-plasmid conjugative transfer. J Bacteriol 180:6039–6042PubMedPubMedCentralGoogle Scholar
  126. Savvides SN et al (2003) VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J 22:1969–1980CrossRefPubMedPubMedCentralGoogle Scholar
  127. Schroder G, Lanka E (2005) The mating pair formation system of conjugative plasmids—a versatile secretion machinery for transfer of proteins and DNA. Plasmid 54:1–25CrossRefPubMedGoogle Scholar
  128. Schroder G et al (2002) TraG-like proteins of DNA transfer systems and of the Helicobacter pylori type IV secretion system: inner membrane gate for exported substrates? J Bacteriol 184:2767–2779CrossRefPubMedPubMedCentralGoogle Scholar
  129. Segal G, Shuman HA (1999a) Legionella pneumophila utilizes the same genes to multiply within Acanthamoeba castellanii and human macrophages. Infect Immun 67:2117–2124Google Scholar
  130. Segal G, Shuman HA (1999b) Possible origin of the Legionella pneumophila virulence genes and their relation to Coxiella burnetii. Mol Microbiol 33:669-667-670CrossRefPubMedGoogle Scholar
  131. Segal G, Purcell M, Schuman HA (1998) Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc Natl Acad Sci U S A 95:1669–1674CrossRefPubMedPubMedCentralGoogle Scholar
  132. Segal G, Feldman M, Zusman T (2005) The Icm/Dot type-IV secretion systems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol Rev 29:65–81CrossRefPubMedGoogle Scholar
  133. Seshadri R et al (2003) Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc Natl Acad Sci U S A 100:5455–5460.  https://doi.org/10.1073/pnas.0931379100CrossRefPubMedPubMedCentralGoogle Scholar
  134. Sexton JA, Vogel JP (2002) Type IVB secretion by intracellular pathogens. Traffic 3:178–185CrossRefPubMedGoogle Scholar
  135. Sexton JA, Miller JL, Yoneda A, Kehl-Fie TE, Vogel JP (2004a) Legionella pneumophila DotU and IcmF are required for stability of the Dot/Icm complex. Infect Immun 72:5983–5992CrossRefPubMedPubMedCentralGoogle Scholar
  136. Sexton JA, Pinkner JS, Roth R, Heuser JE, Hultgren SJ, Vogel JP (2004b) The Legionella pneumophila PilT homologue DotB exhibits ATPase activity that is critical for intracellular growth. J Bacteriol 186:1658–1666CrossRefPubMedPubMedCentralGoogle Scholar
  137. Sherwood RK, Roy CR (2016) Autophagy evasion and endoplasmic reticulum subversion: the yin and yang of Legionella intracellular infection. Annu Rev Microbiol 70:413–433.  https://doi.org/10.1146/annurev-micro-102215-095557CrossRefPubMedGoogle Scholar
  138. Silverman PM, Clarke MB (2010) New insights into F-pilus structure, dynamics, and function. Integr Biol (Camb) 2:25–31.  https://doi.org/10.1039/b917761bCrossRefGoogle Scholar
  139. Souza DP, Andrade MO, Alvarez-Martinez CE, Arantes GM, Farah CS, Salinas RK (2011) A component of the Xanthomonadaceae type IV secretion system combines a VirB7 motif with a N0 domain found in outer membrane transport proteins. PLoS Pathog 7:e1002031.  https://doi.org/10.1371/journal.ppat.1002031 (PPATHOGENS-D-10-00184 [pii])CrossRefPubMedPubMedCentralGoogle Scholar
  140. Souza DP et al (2015) Bacterial killing via a type IV secretion system. Nat Commun 6:6453.  https://doi.org/10.1038/ncomms7453CrossRefPubMedGoogle Scholar
  141. Stingl K, Muller S, Scheidgen-Kleyboldt G, Clausen M, Maier B (2010) Composite system mediates two-step DNA uptake into Helicobacter pylori. Proc Natl Acad Sci U S A 107:1184–1189.  https://doi.org/10.1073/pnas.0909955107CrossRefPubMedPubMedCentralGoogle Scholar
  142. Sutherland MC, Nguyen TL, Tseng V, Vogel JP (2012) The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates. PLoS Pathog 8:e1002910.  https://doi.org/10.1371/journal.ppat.1002910CrossRefPubMedPubMedCentralGoogle Scholar
  143. Sutherland MC, Binder KA, Cualing PY, Vogel JP (2013) Reassessing the role of DotF in the Legionella pneumophila type IV secretion system. PLoS ONE 8:e65529.  https://doi.org/10.1371/journal.pone.0065529CrossRefPubMedPubMedCentralGoogle Scholar
  144. Tegtmeyer N, Wessler S, Necchi V, Rohde M, Harrer A, Rau TT, Asche CI, Boehm M, Loessner M, Figueiredo C, Naumann M, Palmisano R, Solcia E, Ricci V, Backert S (2017) A unique basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori. Cell Host Microbe 22(552–560):e5.  https://doi.org/10.1016/j.chom.2017.09.005CrossRefGoogle Scholar
  145. Terradot L, Waksman G (2011) Architecture of the Helicobacter pylori Cag-type IV secretion system. FEBS J 278:1213–1222.  https://doi.org/10.1111/j.1742-4658.2011.08037.xCrossRefPubMedGoogle Scholar
  146. Thanassi DG, Bliska JB, Christie PJ (2012) Surface organelles assembled by secretion systems of Gram-negative bacteria: diversity in structure and function. FEMS Microbiol Rev 36:1046–1082.  https://doi.org/10.1111/j.1574-6976.2012.00342.xCrossRefPubMedPubMedCentralGoogle Scholar
  147. VanRheenen SM, Dumenil G, Isberg RR (2004) IcmF and DotU are required for optimal effector translocation and trafficking of the Legionella pneumophila vacuole. Infect Immun 72:5972–5982CrossRefPubMedPubMedCentralGoogle Scholar
  148. Vincent CD, Vogel JP (2006) The Legionella pneumophila IcmS-LvgA protein complex is important for Dot/Icm-dependent intracellular growth. Mol Microbiol 61:596–613CrossRefPubMedGoogle Scholar
  149. Vincent CD, Friedman JR, Jeong KC, Buford EC, Miller JL, Vogel JP (2006) Identification of the core transmembrane complex of the Legionella Dot/Icm type IV secretion system. Mol Microbiol 62:1278–1291CrossRefPubMedGoogle Scholar
  150. Vincent CD, Friedman JR, Jeong KC, Sutherland MC, Vogel JP (2012) Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system. Mol Microbiol 85:378–391.  https://doi.org/10.1111/j.1365-2958.2012.08118.xCrossRefPubMedPubMedCentralGoogle Scholar
  151. Vogel JP, Isberg RR (1999) Cell biology of Legionella pneumophila. Curr Opin Microbiol 2:30–34CrossRefPubMedGoogle Scholar
  152. Vogel JP, Andrews HL, Wong SK, Isberg RR (1998) Conjugative transfer by the virulence system of Legionella pneumophila. Science 279:873–876CrossRefPubMedGoogle Scholar
  153. Voth DE, Broederdorf LJ, Graham JG (2012) Bacterial type IV secretion systems: versatile virulence machines. Future Microbiol 7:241–257.  https://doi.org/10.2217/fmb.11.150CrossRefPubMedPubMedCentralGoogle Scholar
  154. Watarai M, Andrews HL, Isberg R (2000) Formation of a fibrous structure on the surface of Legionella pneumophila associated with exposure of DotH and DotO proteins after intracellular growth. Mol Microbiol 39:313–329CrossRefGoogle Scholar
  155. Watarai M, Derre I, Kirby J, Growney JD, Dietrich WF, Isberg RR (2001) Legionella pneumophila is internalized by a macropinocytotic uptake pathway controlled by the Dot/Icm system and the mouse Lgn1. locus. J Exp Med 194:1081–1096CrossRefPubMedPubMedCentralGoogle Scholar
  156. Weber MM et al (2013) Identification of Coxiella burnetii type IV secretion substrates required for intracellular replication and Coxiella-containing vacuole formation. J Bacteriol 195:3914–3924.  https://doi.org/10.1128/JB.00071-13CrossRefPubMedPubMedCentralGoogle Scholar
  157. Whitaker N, Chen Y, Jakubowski SJ, Sarkar MK, Li F, Christie PJ (2015) The all-alpha domains of coupling proteins from the Agrobacterium tumefaciens VirB/VirD4 and Enterococcus faecalis pCF10-Encoded type IV secretion systems confer specificity to binding of cognate DNA substrates. J Bacteriol 197:2335–2349.  https://doi.org/10.1128/JB.00189-15CrossRefPubMedPubMedCentralGoogle Scholar
  158. Whitaker N et al (2016) Chimeric coupling proteins mediate transfer of heterologous type IV effectors through the Escherichia coli pKM101-encoded conjugation machine. J Bacteriol 198:2701–2718.  https://doi.org/10.1128/JB.00378-16CrossRefPubMedPubMedCentralGoogle Scholar
  159. Xu J et al (2017) Structural insights into the roles of the IcmS-IcmW complex in the type IVb secretion system of Legionella pneumophila. Proc Natl Acad Sci U S A.  https://doi.org/10.1073/pnas.1706883115CrossRefPubMedPubMedCentralGoogle Scholar
  160. Yerushalmi G, Zusman T, Segal G (2005) Additive effect on intracellular growth by Legionella pneumophila Icm/Dot proteins containing a lipobox motif. Infect Immun 73:7578–7587.  https://doi.org/10.1128/IAI.73.11.7578-7587.2005CrossRefPubMedPubMedCentralGoogle Scholar
  161. Yoshida T, Kim SR, Komano T (1999) Twelve pil genes are required for biogenesis of the R64 thin pilus. J Bacteriol 181:2038–2043PubMedPubMedCentralGoogle Scholar
  162. Zamboni DS, McGrath S, Rabinovitch M, Roy CR (2003) Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system. Mol Microbiol 49:965–976CrossRefPubMedGoogle Scholar
  163. Zuckman DM, Hung JB, Roy CR (1999) Pore-forming activity is not sufficient for Legionella pneumophila phagosome trafficking and intracellular growth. Mol Microbiol 32:990–1001CrossRefPubMedGoogle Scholar
  164. Zusman T, Yerushalmi G, Segal G (2003) Functional similarities between the icm/dot pathogenesis systems of Coxiella burnetii and Legionella pneumophila. Infect Immun 71:3714–3723CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Peter J. Christie
    • 1
  • Laura Gomez Valero
    • 2
    • 3
  • Carmen Buchrieser
    • 2
    • 3
  1. 1.Department of Microbiology and Molecular GeneticsMcGovern Medical SchoolHoustonUSA
  2. 2.Institut PasteurParisFrance
  3. 3.CNRS, UMR 3525ParisFrance

Personalised recommendations