1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Architecture, Function, and Substrates of the Type II Secretion System

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Konstantin V. Korotkov1, and Maria Sandkvist2
  • Editors: Eric Cascales3, Peter J. Christie4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40506; 2: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109; 3: CNRS Aix-Marseille Université, Mediterranean Institute of Microbiology, Marseille, France; 4: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas
  • Received 24 October 2018 Accepted 21 December 2018 Published 15 February 2019
  • Address correspondence to Konstantin V. Korotkov, [email protected]; Maria Sandkvist, [email protected]
image of Architecture, Function, and Substrates of the Type II Secretion System
    Preview this reference work article:
    Zoom in
    Zoomout

    Architecture, Function, and Substrates of the Type II Secretion System, Page 1 of 2

    | /docserver/preview/fulltext/ecosalplus/8/2/ESP-0034-2018-1.gif /docserver/preview/fulltext/ecosalplus/8/2/ESP-0034-2018-2.gif
  • Abstract:

    The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.

  • Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018

Article Version

This article is an updated version of the following content:

References

1. Abby SS, Cury J, Guglielmini J, Néron B, Touchon M, Rocha EP. 2016. Identification of protein secretion systems in bacterial genomes. Sci Rep 6:23080. http://dx.doi.org/10.1038/srep23080.
2. Cianciotto NP, White RC. 2017. Expanding role of type II secretion in bacterial pathogenesis and beyond. Infect Immun 85:e00014-17. http://dx.doi.org/10.1128/IAI.00014-17.
3. Korotkov KV, Sandkvist M, Hol WGJ. 2012. The type II secretion system: biogenesis, molecular architecture and mechanism. Nat Rev Microbiol 10:336–351. http://dx.doi.org/10.1038/nrmicro2762.
4. Sikora AE. 2013. Proteins secreted via the type II secretion system: smart strategies of Vibrio cholerae to maintain fitness in different ecological niches. PLoS Pathog 9:e1003126. http://dx.doi.org/10.1371/journal.ppat.1003126.
5. Liles MR, Edelstein PH, Cianciotto NP. 1999. The prepilin peptidase is required for protein secretion by and the virulence of the intracellular pathogen Legionella pneumophila. Mol Microbiol 31:959–970. http://dx.doi.org/10.1046/j.1365-2958.1999.01239.x.
6. Hales LM, Shuman HA. 1999. Legionella pneumophila contains a type II general secretion pathway required for growth in amoebae as well as for secretion of the Msp protease. Infect Immun 67:3662–3666.
7. Rossier O, Cianciotto NP. 2001. Type II protein secretion is a subset of the PilD-dependent processes that facilitate intracellular infection by Legionella pneumophila. Infect Immun 69:2092–2098. http://dx.doi.org/10.1128/IAI.69.4.2092-2098.2001.
8. Nguyen BD, Valdivia RH. 2012. Virulence determinants in the obligate intracellular pathogen Chlamydia trachomatis revealed by forward genetic approaches. Proc Natl Acad Sci U S A 109:1263–1268. http://dx.doi.org/10.1073/pnas.1117884109.
9. Snavely EA, Kokes M, Dunn JD, Saka HA, Nguyen BD, Bastidas RJ, McCafferty DG, Valdivia RH. 2014. Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches. Pathog Dis 71:336–351. http://dx.doi.org/10.1111/2049-632X.12179.
10. McCallum M, Burrows LL, Howell PL. 2018. The dynamic structures of the type IV pilus. Microbiol Spectr 7:PSIB-0006-2018.
11. Sandkvist M, Bagdasarian M, Howard SP, DiRita VJ. 1995. Interaction between the autokinase EpsE and EpsL in the cytoplasmic membrane is required for extracellular secretion in Vibrio cholerae. EMBO J 14:1664–1673. http://dx.doi.org/10.1002/j.1460-2075.1995.tb07155.x.
12. Sandkvist M, Keith JM, Bagdasarian M, Howard SP. 2000. Two regions of EpsL involved in species-specific protein-protein interactions with EpsE and EpsM of the general secretion pathway in Vibrio cholerae. J Bacteriol 182:742–748. http://dx.doi.org/10.1128/JB.182.3.742-748.2000.
13. Py B, Loiseau L, Barras F. 2001. An inner membrane platform in the type II secretion machinery of Gram-negative bacteria. EMBO Rep 2:244–248. http://dx.doi.org/10.1093/embo-reports/kve042.
14. Robien MA, Krumm BE, Sandkvist M, Hol WGJ. 2003. Crystal structure of the extracellular protein secretion NTPase EpsE of Vibrio cholerae. J Mol Biol 333:657–674. http://dx.doi.org/10.1016/j.jmb.2003.07.015.
15. Camberg JL, Sandkvist M. 2005. Molecular analysis of the Vibrio cholerae type II secretion ATPase EpsE. J Bacteriol 187:249–256. http://dx.doi.org/10.1128/JB.187.1.249-256.2005.
16. Abendroth J, Murphy P, Sandkvist M, Bagdasarian M, Hol WGJ. 2005. The X-ray structure of the type II secretion system complex formed by the N-terminal domain of EpsE and the cytoplasmic domain of EpsL of Vibrio cholerae. J Mol Biol 348:845–855. http://dx.doi.org/10.1016/j.jmb.2005.02.061.
17. Camberg JL, Johnson TL, Patrick M, Abendroth J, Hol WGJ, Sandkvist M. 2007. Synergistic stimulation of EpsE ATP hydrolysis by EpsL and acidic phospholipids. EMBO J 26:19–27. http://dx.doi.org/10.1038/sj.emboj.7601481.
18. Arts J, de Groot A, Ball G, Durand E, El Khattabi M, Filloux A, Tommassen J, Koster M. 2007. Interaction domains in the Pseudomonas aeruginosa type II secretory apparatus component XcpS (GspF). Microbiology 153:1582–1592. http://dx.doi.org/10.1099/mic.0.2006/002840-0.
19. Abendroth J, Mitchell DD, Korotkov KV, Johnson TL, Kreger A, Sandkvist M, Hol WGJ. 2009. The three-dimensional structure of the cytoplasmic domains of EpsF from the type 2 secretion system of Vibrio cholerae. J Struct Biol 166:303–315. http://dx.doi.org/10.1016/j.jsb.2009.03.009.
20. Lu C, Turley S, Marionni ST, Park YJ, Lee KK, Patrick M, Shah R, Sandkvist M, Bush MF, Hol WGJ. 2013. Hexamers of the type II secretion ATPase GspE from Vibrio cholerae with increased ATPase activity. Structure 21:1707–1717. http://dx.doi.org/10.1016/j.str.2013.06.027.
21. Lu C, Korotkov KV, Hol WGJ. 2014. Crystal structure of the full-length ATPase GspE from the Vibrio vulnificus type II secretion system in complex with the cytoplasmic domain of GspL. J Struct Biol 187:223–235. http://dx.doi.org/10.1016/j.jsb.2014.07.006.
22. Michel G, Bleves S, Ball G, Lazdunski A, Filloux A. 1998. Mutual stabilization of the XcpZ and XcpY components of the secretory apparatus in Pseudomonas aeruginosa. Microbiology 144:3379–3386. http://dx.doi.org/10.1099/00221287-144-12-3379.
23. Sandkvist M, Hough LP, Bagdasarian MM, Bagdasarian M. 1999. Direct interaction of the EpsL and EpsM proteins of the general secretion apparatus in Vibrio cholerae. J Bacteriol 181:3129–3135.
24. Robert V, Hayes F, Lazdunski A, Michel GP. 2002. Identification of XcpZ domains required for assembly of the secreton of Pseudomonas aeruginosa. J Bacteriol 184:1779–1782. http://dx.doi.org/10.1128/JB.184.6.1779-1782.2002.
25. Abendroth J, Rice AE, McLuskey K, Bagdasarian M, Hol WGJ. 2004. The crystal structure of the periplasmic domain of the type II secretion system protein EpsM from Vibrio cholerae: the simplest version of the ferredoxin fold. J Mol Biol 338:585–596. http://dx.doi.org/10.1016/j.jmb.2004.01.064.
26. Abendroth J, Kreger AC, Hol WGJ. 2009. The dimer formed by the periplasmic domain of EpsL from the type 2 secretion system of Vibrio parahaemolyticus. J Struct Biol 168:313–322. http://dx.doi.org/10.1016/j.jsb.2009.07.022.
27. Lallemand M, Login FH, Guschinskaya N, Pineau C, Effantin G, Robert X, Shevchik VE. 2013. Dynamic interplay between the periplasmic and transmembrane domains of GspL and GspM in the type II secretion system. PLoS One 8:e79562. http://dx.doi.org/10.1371/journal.pone.0079562.
28. Lybarger SR, Johnson TL, Gray MD, Sikora AE, Sandkvist M. 2009. Docking and assembly of the type II secretion complex of Vibrio cholerae. J Bacteriol 191:3149–3161. http://dx.doi.org/10.1128/JB.01701-08.
29. Korotkov KV, Krumm B, Bagdasarian M, Hol WGJ. 2006. Structural and functional studies of EpsC, a crucial component of the type 2 secretion system from Vibrio cholerae. J Mol Biol 363:311–321. http://dx.doi.org/10.1016/j.jmb.2006.08.037.
30. Korotkov KV, Pardon E, Steyaert J, Hol WGJ. 2009. Crystal structure of the N-terminal domain of the secretin GspD from ETEC determined with the assistance of a nanobody. Structure 17:255–265. http://dx.doi.org/10.1016/j.str.2008.11.011.
31. Reichow SL, Korotkov KV, Hol WGJ, Gonen T. 2010. Structure of the cholera toxin secretion channel in its closed state. Nat Struct Mol Biol 17:1226–1232. http://dx.doi.org/10.1038/nsmb.1910.
32. Korotkov KV, Johnson TL, Jobling MG, Pruneda J, Pardon E, Héroux A, Turley S, Steyaert J, Holmes RK, Sandkvist M, Hol WGJ. 2011. Structural and functional studies on the interaction of GspC and GspD in the type II secretion system. PLoS Pathog 7:e1002228. http://dx.doi.org/10.1371/journal.ppat.1002228.
33. Wang X, Pineau C, Gu S, Guschinskaya N, Pickersgill RW, Shevchik VE. 2012. Cysteine scanning mutagenesis and disulfide mapping analysis of arrangement of GspC and GspD protomers within the type 2 secretion system. J Biol Chem 287:19082–19093. http://dx.doi.org/10.1074/jbc.M112.346338.
34. Yan Z, Yin M, Xu D, Zhu Y, Li X. 2017. Structural insights into the secretin translocation channel in the type II secretion system. Nat Struct Mol Biol 24:177–183. http://dx.doi.org/10.1038/nsmb.3350.
35. Hay ID, Belousoff MJ, Lithgow T. 2017. Structural basis of type 2 secretion system engagement between the inner and outer bacterial membranes. mBio 8:e01344-17. http://dx.doi.org/10.1128/mBio.01344-17.
36. Hay ID, Belousoff MJ, Dunstan RA, Bamert RS, Lithgow T. 2018. Structure and membrane topography of the Vibrio-type secretin complex from the type 2 secretion system of enteropathogenic Escherichia coli. J Bacteriol 200:e00521-17.
37. Yin M, Yan Z, Li X. 2018. Structural insight into the assembly of the type II secretion system pilotin-secretin complex from enterotoxigenic Escherichia coli. Nat Microbiol 3:581–587. http://dx.doi.org/10.1038/s41564-018-0148-0.
38. Majewski DD, Worrall LJ, Strynadka NC. 2018. Secretins revealed: structural insights into the giant gated outer membrane portals of bacteria. Curr Opin Struct Biol 51:61–72. http://dx.doi.org/10.1016/j.sbi.2018.02.008.
39. Possot OM, Vignon G, Bomchil N, Ebel F, Pugsley AP. 2000. Multiple interactions between pullulanase secreton components involved in stabilization and cytoplasmic membrane association of PulE. J Bacteriol 182:2142–2152. http://dx.doi.org/10.1128/JB.182.8.2142-2152.2000.
40. Johnson TL, Waack U, Smith S, Mobley H, Sandkvist M. 2016. Acinetobacter baumannii is dependent on the type II secretion system and its substrate LipA for lipid utilization and in vivo fitness. J Bacteriol 198:711–719. http://dx.doi.org/10.1128/JB.00622-15.
41. Lee HM, Wang KC, Liu YL, Yew HY, Chen LY, Leu WM, Chen DC, Hu NT. 2000. Association of the cytoplasmic membrane protein XpsN with the outer membrane protein XpsD in the type II protein secretion apparatus of Xanthomonas campestris pv. campestris. J Bacteriol 182:1549–1557. http://dx.doi.org/10.1128/JB.182.6.1549-1557.2000.
42. Li G, Miller A, Bull H, Howard SP. 2011. Assembly of the type II secretion system: identification of ExeA residues critical for peptidoglycan binding and secretin multimerization. J Bacteriol 193:197–204. http://dx.doi.org/10.1128/JB.00882-10.
43. Strozen TG, Stanley H, Gu Y, Boyd J, Bagdasarian M, Sandkvist M, Howard SP. 2011. Involvement of the GspAB complex in assembly of the type II secretion system secretin of Aeromonas and Vibrio species. J Bacteriol 193:2322–2331. http://dx.doi.org/10.1128/JB.01413-10.
44. Vanderlinde EM, Strozen TG, Hernández SB, Cava F, Howard SP. 2017. Alterations in peptidoglycan cross-linking suppress the secretin assembly defect caused by mutation of GspA in the type II secretion system. J Bacteriol 199:e00617-17. http://dx.doi.org/10.1128/JB.00617-16.
45. Sauvonnet N, Vignon G, Pugsley AP, Gounon P. 2000. Pilus formation and protein secretion by the same machinery in Escherichia coli. EMBO J 19:2221–2228. http://dx.doi.org/10.1093/emboj/19.10.2221.
46. Durand E, Bernadac A, Ball G, Lazdunski A, Sturgis JN, Filloux A. 2003. Type II protein secretion in Pseudomonas aeruginosa: the pseudopilus is a multifibrillar and adhesive structure. J Bacteriol 185:2749–2758. http://dx.doi.org/10.1128/JB.185.9.2749-2758.2003.
47. Yanez ME, Korotkov KV, Abendroth J, Hol WGJ. 2008. Structure of the minor pseudopilin EpsH from the type 2 secretion system of Vibrio cholerae. J Mol Biol 377:91–103. http://dx.doi.org/10.1016/j.jmb.2007.08.041.
48. Korotkov KV, Hol WGJ. 2008. Structure of the GspK-GspI-GspJ complex from the enterotoxigenic Escherichia coli type 2 secretion system. Nat Struct Mol Biol 15:462–468. http://dx.doi.org/10.1038/nsmb.1426.
49. Douzi B, Durand E, Bernard C, Alphonse S, Cambillau C, Filloux A, Tegoni M, Voulhoux R. 2009. The XcpV/GspI pseudopilin has a central role in the assembly of a quaternary complex within the T2SS pseudopilus. J Biol Chem 284:34580–34589. http://dx.doi.org/10.1074/jbc.M109.042366.
50. López-Castilla A, Thomassin JL, Bardiaux B, Zheng W, Nivaskumar M, Yu X, Nilges M, Egelman EH, Izadi-Pruneyre N, Francetic O. 2017. Structure of the calcium-dependent type 2 secretion pseudopilus. Nat Microbiol 2:1686–1695. http://dx.doi.org/10.1038/s41564-017-0041-2.
51. Pugsley AP, Dupuy B. 1992. An enzyme with type IV prepilin peptidase activity is required to process components of the general extracellular protein secretion pathway of Klebsiella oxytoca. Mol Microbiol 6:751–760. http://dx.doi.org/10.1111/j.1365-2958.1992.tb01525.x. [PubMed]
52. Pugsley AP. 1993. Processing and methylation of PuIG, a pilin-like component of the general secretory pathway of Klebsiella oxytoca. Mol Microbiol 9:295–308. http://dx.doi.org/10.1111/j.1365-2958.1993.tb01691.x. [PubMed]
53. Nunn DN, Lory S. 1993. Cleavage, methylation, and localization of the Pseudomonas aeruginosa export proteins XcpT, -U, -V, and -W. J Bacteriol 175:4375–4382. http://dx.doi.org/10.1128/jb.175.14.4375-4382.1993.
54. Pugsley AP, Kornacker MG, Poquet I. 1991. The general protein-export pathway is directly required for extracellular pullulanase secretion in Escherichia coli K12. Mol Microbiol 5:343–352. http://dx.doi.org/10.1111/j.1365-2958.1991.tb02115.x. [PubMed]
55. He SY, Schoedel C, Chatterjee AK, Collmer A. 1991. Extracellular secretion of pectate lyase by the Erwinia chrysanthemi out pathway is dependent upon Sec-mediated export across the inner membrane. J Bacteriol 173:4310–4317. http://dx.doi.org/10.1128/jb.173.14.4310-4317.1991.
56. Voulhoux R, Ball G, Ize B, Vasil ML, Lazdunski A, Wu LF, Filloux A. 2001. Involvement of the twin-arginine translocation system in protein secretion via the type II pathway. EMBO J 20:6735–6741. http://dx.doi.org/10.1093/emboj/20.23.6735. [PubMed]
57. Ball G, Antelmann H, Imbert PR, Gimenez MR, Voulhoux R, Ize B. 2016. Contribution of the twin arginine translocation system to the exoproteome of Pseudomonas aeruginosa. Sci Rep 6:27675. http://dx.doi.org/10.1038/srep27675. [PubMed]
58. Hirst TR, Holmgren J. 1987. Transient entry of enterotoxin subunits into the periplasm occurs during their secretion from Vibrio cholerae. J Bacteriol 169:1037–1045. http://dx.doi.org/10.1128/jb.169.3.1037-1045.1987.
59. Hirst TR, Holmgren J. 1987. Conformation of protein secreted across bacterial outer membranes: a study of enterotoxin translocation from Vibrio cholerae. Proc Natl Acad Sci U S A 84:7418–7422. http://dx.doi.org/10.1073/pnas.84.21.7418.
60. Hardy SJ, Holmgren J, Johansson S, Sanchez J, Hirst TR. 1988. Coordinated assembly of multisubunit proteins: oligomerization of bacterial enterotoxins in vivo and in vitro. Proc Natl Acad Sci U S A 85:7109–7113. http://dx.doi.org/10.1073/pnas.85.19.7109. [PubMed]
61. Pugsley AP. 1992. Translocation of a folded protein across the outer membrane in Escherichia coli. Proc Natl Acad Sci U S A 89:12058–12062. http://dx.doi.org/10.1073/pnas.89.24.12058. [PubMed]
62. Poquet I, Faucher D, Pugsley AP. 1993. Stable periplasmic secretion intermediate in the general secretory pathway of Escherichia coli. EMBO J 12:271–278. http://dx.doi.org/10.1002/j.1460-2075.1993.tb05653.x. [PubMed]
63. Hardie KR, Schulze A, Parker MW, Buckley JT. 1995. Vibrio spp. secrete proaerolysin as a folded dimer without the need for disulphide bond formation. Mol Microbiol 17:1035–1044. http://dx.doi.org/10.1111/j.1365-2958.1995.mmi_17061035.x. [PubMed]
64. Braun P, Tommassen J, Filloux A. 1996. Role of the propeptide in folding and secretion of elastase of Pseudomonas aeruginosa. Mol Microbiol 19:297–306. http://dx.doi.org/10.1046/j.1365-2958.1996.381908.x. [PubMed]
65. Voulhoux R, Taupiac MP, Czjzek M, Beaumelle B, Filloux A. 2000. Influence of deletions within domain II of exotoxin A on its extracellular secretion from Pseudomonas aeruginosa. J Bacteriol 182:4051–4058. http://dx.doi.org/10.1128/JB.182.14.4051-4058.2000. [PubMed]
66. Häse CC, Finkelstein RA. 1991. Cloning and nucleotide sequence of the Vibrio cholerae hemagglutinin/protease (HA/protease) gene and construction of an HA/protease-negative strain. J Bacteriol 173:3311–3317. http://dx.doi.org/10.1128/jb.173.11.3311-3317.1991. [PubMed]
67. McIver KS, Kessler E, Olson JC, Ohman DE. 1995. The elastase propeptide functions as an intramolecular chaperone required for elastase activity and secretion in Pseudomonas aeruginosa. Mol Microbiol 18:877–889. http://dx.doi.org/10.1111/j.1365-2958.1995.18050877.x. [PubMed]
68. Gadwal S, Korotkov KV, Delarosa JR, Hol WGJ, Sandkvist M. 2014. Functional and structural characterization of Vibrio cholerae extracellular serine protease B, VesB. J Biol Chem 289:8288–8298. http://dx.doi.org/10.1074/jbc.M113.525261. [PubMed]
69. Hobson AH, Buckley CM, Aamand JL, Jørgensen ST, Diderichsen B, McConnell DJ. 1993. Activation of a bacterial lipase by its chaperone. Proc Natl Acad Sci U S A 90:5682–5686. http://dx.doi.org/10.1073/pnas.90.12.5682. [PubMed]
70. Martínez A, Ostrovsky P, Nunn DN. 1999. LipC, a second lipase of Pseudomonas aeruginosa, is LipB and Xcp dependent and is transcriptionally regulated by pilus biogenesis components. Mol Microbiol 34:317–326. http://dx.doi.org/10.1046/j.1365-2958.1999.01601.x. [PubMed]
71. Pauwels K, Lustig A, Wyns L, Tommassen J, Savvides SN, Van Gelder P. 2006. Structure of a membrane-based steric chaperone in complex with its lipase substrate. Nat Struct Mol Biol 13:374–375. http://dx.doi.org/10.1038/nsmb1065. [PubMed]
72. Coulthurst SJ, Lilley KS, Hedley PE, Liu H, Toth IK, Salmond GP. 2008. DsbA plays a critical and multifaceted role in the production of secreted virulence factors by the phytopathogen Erwinia carotovora subsp. atroseptica. J Biol Chem 283:23739–23753. http://dx.doi.org/10.1074/jbc.M801829200. [PubMed]
73. Harding CM, Kinsella RL, Palmer LD, Skaar EP, Feldman MF. 2016. Medically relevant Acinetobacter species require a type II secretion system and specific membrane-associated chaperones for the export of multiple substrates and full virulence. PLoS Pathog 12:e1005391. http://dx.doi.org/10.1371/journal.ppat.1005391. [PubMed]
74. Kinsella RL, Lopez J, Palmer LD, Salinas ND, Skaar EP, Tolia NH, Feldman MF. 2017. Defining the interaction of the protease CpaA with its type II secretion chaperone CpaB and its contribution to virulence in Acinetobacter species. J Biol Chem 292:19628–19638. http://dx.doi.org/10.1074/jbc.M117.808394. [PubMed]
75. Pugsley AP, Chapon C, Schwartz M. 1986. Extracellular pullulanase of Klebsiella pneumoniae is a lipoprotein. J Bacteriol 166:1083–1088. http://dx.doi.org/10.1128/jb.166.3.1083-1088.1986. [PubMed]
76. Baldi DL, Higginson EE, Hocking DM, Praszkier J, Cavaliere R, James CE, Bennett-Wood V, Azzopardi KI, Turnbull L, Lithgow T, Robins-Browne RM, Whitchurch CB, Tauschek M. 2012. The type II secretion system and its ubiquitous lipoprotein substrate, SslE, are required for biofilm formation and virulence of enteropathogenic Escherichia coli. Infect Immun 80:2042–2052. http://dx.doi.org/10.1128/IAI.06160-11. [PubMed]
77. East A, Mechaly AE, Huysmans GHM, Bernarde C, Tello-Manigne D, Nadeau N, Pugsley AP, Buschiazzo A, Alzari PM, Bond PJ, Francetic O. 2016. Structural basis of pullulanase membrane binding and secretion revealed by X-ray crystallography, molecular dynamics and biochemical analysis. Structure 24:92–104. http://dx.doi.org/10.1016/j.str.2015.10.023. [PubMed]
78. Zückert WR. 2014. Secretion of bacterial lipoproteins: through the cytoplasmic membrane, the periplasm and beyond. Biochim Biophys Acta 1843:1509–1516. http://dx.doi.org/10.1016/j.bbamcr.2014.04.022. [PubMed]
79. d’Enfert C, Chapon C, Pugsley AP. 1987. Export and secretion of the lipoprotein pullulanase by Klebsiella pneumoniae. Mol Microbiol 1:107–116. http://dx.doi.org/10.1111/j.1365-2958.1987.tb00534.x. [PubMed]
80. Horstman AL, Kuehn MJ. 2002. Bacterial surface association of heat-labile enterotoxin through lipopolysaccharide after secretion via the general secretory pathway. J Biol Chem 277:32538–32545. http://dx.doi.org/10.1074/jbc.M203740200. [PubMed]
81. Horstman AL, Bauman SJ, Kuehn MJ. 2004. Lipopolysaccharide 3-deoxy- d-manno-octulosonic acid (Kdo) core determines bacterial association of secreted toxins. J Biol Chem 279:8070–8075. http://dx.doi.org/10.1074/jbc.M308633200. [PubMed]
82. Ferrandez Y, Condemine G. 2008. Novel mechanism of outer membrane targeting of proteins in Gram-negative bacteria. Mol Microbiol 69:1349–1357. http://dx.doi.org/10.1111/j.1365-2958.2008.06366.x. [PubMed]
83. Haft DH, Varghese N. 2011. GlyGly-CTERM and rhombosortase: a C-terminal protein processing signal in a many-to-one pairing with a rhomboid family intramembrane serine protease. PLoS One 6:e28886. http://dx.doi.org/10.1371/journal.pone.0028886. [PubMed]
84. Gadwal S, Johnson TL, Remmer H, Sandkvist M. 2018. C-terminal processing of GlyGly-CTERM containing proteins by rhombosortase in Vibrio cholerae. PLoS Pathog 14:e1007341. http://dx.doi.org/10.1371/journal.ppat.1007341. [PubMed]
85. Sandkvist M, Michel LO, Hough LP, Morales VM, Bagdasarian M, Koomey M, DiRita VJ, Bagdasarian M. 1997. General secretion pathway ( eps) genes required for toxin secretion and outer membrane biogenesis in Vibrio cholerae. J Bacteriol 179:6994–7003. http://dx.doi.org/10.1128/jb.179.22.6994-7003.1997. [PubMed]
86. Tauschek M, Gorrell RJ, Strugnell RA, Robins-Browne RM. 2002. Identification of a protein secretory pathway for the secretion of heat-labile enterotoxin by an enterotoxigenic strain of Escherichia coli. Proc Natl Acad Sci U S A 99:7066–7071. http://dx.doi.org/10.1073/pnas.092152899. [PubMed]
87. Lindeberg M, Collmer A. 1992. Analysis of eight out genes in a cluster required for pectic enzyme secretion by Erwinia chrysanthemi: sequence comparison with secretion genes from other gram-negative bacteria. J Bacteriol 174:7385–7397. http://dx.doi.org/10.1128/jb.174.22.7385-7397.1992. [PubMed]
88. Kagami Y, Ratliff M, Surber M, Martinez A, Nunn DN. 1998. Type II protein secretion by Pseudomonas aeruginosa: genetic suppression of a conditional mutation in the pilin-like component XcpT by the cytoplasmic component XcpR. Mol Microbiol 27:221–233. http://dx.doi.org/10.1046/j.1365-2958.1998.00679.x. [PubMed]
89. Sikora AE, Lybarger SR, Sandkvist M. 2007. Compromised outer membrane integrity in Vibrio cholerae type II secretion mutants. J Bacteriol 189:8484–8495. http://dx.doi.org/10.1128/JB.00583-07. [PubMed]
90. Park BR, Zielke RA, Wierzbicki IH, Mitchell KC, Withey JH, Sikora AE. 2015. A metalloprotease secreted by the type II secretion system links Vibrio cholerae with collagen. J Bacteriol 197:1051–1064. http://dx.doi.org/10.1128/JB.02329-14. [PubMed]
91. White RC, Gunderson FF, Tyson JY, Richardson KH, Portlock TJ, Garnett JA, Cianciotto NP. 2018. Type II secretion-dependent aminopeptidase LapA and acyltransferase PlaC are redundant for nutrient acquisition during Legionella pneumophila intracellular infection of amoebas. mBio 9:e00528-18. http://dx.doi.org/10.1128/mBio.00528-18. [PubMed]
92. Wilton M, Halverson TWR, Charron-Mazenod L, Parkins MD, Lewenza S. 2018. Secreted phosphatase and deoxyribonuclease are required by Pseudomonas aeruginosa to defend against neutrophil extracellular traps. Infect Immun 86:e00403-18. http://dx.doi.org/10.1128/IAI.00403-18. [PubMed]
93. Chapon V, Czjzek M, El Hassouni M, Py B, Juy M, Barras F. 2001. Type II protein secretion in gram-negative pathogenic bacteria: the study of the structure/secretion relationships of the cellulase Cel5 (formerly EGZ) from Erwinia chrysanthemi. J Mol Biol 310:1055–1066. http://dx.doi.org/10.1006/jmbi.2001.4787. [PubMed]
94. Silva AJ, Pham K, Benitez JA. 2003. Haemagglutinin/protease expression and mucin gel penetration in El Tor biotype Vibrio cholerae. Microbiology 149:1883–1891. http://dx.doi.org/10.1099/mic.0.26086-0. [PubMed]
95. Luo Q, Kumar P, Vickers TJ, Sheikh A, Lewis WG, Rasko DA, Sistrunk J, Fleckenstein JM. 2014. Enterotoxigenic Escherichia coli secretes a highly conserved mucin-degrading metalloprotease to effectively engage intestinal epithelial cells. Infect Immun 82:509–521. http://dx.doi.org/10.1128/IAI.01106-13. [PubMed]
96. Hews CL, Tran SL, Wegmann U, Brett B, Walsham ADS, Kavanaugh D, Ward NJ, Juge N, Schüller S. 2017. The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo. Cell Microbiol 19:e12717. http://dx.doi.org/10.1111/cmi.12717. [PubMed]
97. Kooi C, Sokol PA. 2009. Burkholderia cenocepacia zinc metalloproteases influence resistance to antimicrobial peptides. Microbiology 155:2818–2825. http://dx.doi.org/10.1099/mic.0.028969-0. [PubMed]
98. McCoy-Simandle K, Stewart CR, Dao J, DebRoy S, Rossier O, Bryce PJ, Cianciotto NP. 2011. Legionella pneumophila type II secretion dampens the cytokine response of infected macrophages and epithelia. Infect Immun 79:1984–1997. http://dx.doi.org/10.1128/IAI.01077-10. [PubMed]
99. Mallama CA, McCoy-Simandle K, Cianciotto NP. 2017. The type II secretion system of Legionella pneumophila dampens the MyD88 and Toll-like receptor 2 signaling pathway in infected human macrophages. Infect Immun 85:e00897-16. http://dx.doi.org/10.1128/IAI.00897-16. [PubMed]
100. Lathem WW, Grys TE, Witowski SE, Torres AG, Kaper JB, Tarr PI, Welch RA. 2002. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Mol Microbiol 45:277–288. http://dx.doi.org/10.1046/j.1365-2958.2002.02997.x.
101. Szabady RL, Lokuta MA, Walters KB, Huttenlocher A, Welch RA. 2009. Modulation of neutrophil function by a secreted mucinase of Escherichia coli O157:H7. PLoS Pathog 5:e1000320. http://dx.doi.org/10.1371/journal.ppat.1000320. [PubMed]
102. Tilley D, Law R, Warren S, Samis JA, Kumar A. 2014. CpaA a novel protease from Acinetobacter baumannii clinical isolates deregulates blood coagulation. FEMS Microbiol Lett 356:53–61. http://dx.doi.org/10.1111/1574-6968.12496. [PubMed]
103. Waack U, Warnock M, Yee A, Huttinger Z, Smith S, Kumar A, Deroux A, Ginsburg D, Mobley HLT, Lawrence DA, Sandkvist M. 2018. CpaA is a glycan-specific adamalysin-like protease secreted by Acinetobacter baumannii that inactivates coagulation factor XII. mBio 9:e01606-18. http://dx.doi.org/10.1128/mBio.01606-18. [PubMed]
104. Overhage J, Lewenza S, Marr AK, Hancock RE. 2007. Identification of genes involved in swarming motility using a Pseudomonas aeruginosa PAO1 mini-Tn5- lux mutant library. J Bacteriol 189:2164–2169. http://dx.doi.org/10.1128/JB.01623-06. [PubMed]
105. Duncan C, Prashar A, So J, Tang P, Low DE, Terebiznik M, Guyard C. 2011. Lcl of Legionella pneumophila is an immunogenic GAG binding adhesin that promotes interactions with lung epithelial cells and plays a crucial role in biofilm formation. Infect Immun 79:2168–2181. http://dx.doi.org/10.1128/IAI.01304-10. [PubMed]
106. Johnson TL, Fong JC, Rule C, Rogers A, Yildiz FH, Sandkvist M. 2014. The type II secretion system delivers matrix proteins for biofilm formation by Vibrio cholerae. J Bacteriol 196:4245–4252. http://dx.doi.org/10.1128/JB.01944-14. [PubMed]
107. Fong JNC, Yildiz FH. 2015. Biofilm matrix proteins. Microbiol Spectr 3:MB-0004-2014. http://dx.doi.org/10.1128/microbiolspec.MB-0004-2014. [PubMed]
108. Fong JC, Rogers A, Michael AK, Parsley NC, Cornell WC, Lin YC, Singh PK, Hartmann R, Drescher K, Vinogradov E, Dietrich LE, Partch CL, Yildiz FH. 2017. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. eLife 6:e26163. http://dx.doi.org/10.7554/eLife.26163. [PubMed]
109. Ennouri H, d’Abzac P, Hakil F, Branchu P, Naïtali M, Lomenech AM, Oueslati R, Desbrières J, Sivadon P, Grimaud R. 2017. The extracellular matrix of the oleolytic biofilms of Marinobacter hydrocarbonoclasticus comprises cytoplasmic proteins and T2SS effectors that promote growth on hydrocarbons and lipids. Environ Microbiol 19:159–173. http://dx.doi.org/10.1111/1462-2920.13547. [PubMed]
110. Nouwen N, Ranson N, Saibil H, Wolpensinger B, Engel A, Ghazi A, Pugsley AP. 1999. Secretin PulD: association with pilot PulS, structure, and ion-conducting channel formation. Proc Natl Acad Sci U S A 96:8173–8177. http://dx.doi.org/10.1073/pnas.96.14.8173. [PubMed]
111. Nouwen N, Stahlberg H, Pugsley AP, Engel A. 2000. Domain structure of secretin PulD revealed by limited proteolysis and electron microscopy. EMBO J 19:2229–2236. http://dx.doi.org/10.1093/emboj/19.10.2229. [PubMed]
112. Chami M, Guilvout I, Gregorini M, Rémigy HW, Müller SA, Valerio M, Engel A, Pugsley AP, Bayan N. 2005. Structural insights into the secretin PulD and its trypsin-resistant core. J Biol Chem 280:37732–37741. http://dx.doi.org/10.1074/jbc.M504463200. [PubMed]
113. Tosi T, Estrozi LF, Job V, Guilvout I, Pugsley AP, Schoehn G, Dessen A. 2014. Structural similarity of secretins from type II and type III secretion systems. Structure 22:1348–1355. http://dx.doi.org/10.1016/j.str.2014.07.005. [PubMed]
114. Dunstan RA, Heinz E, Wijeyewickrema LC, Pike RN, Purcell AW, Evans TJ, Praszkier J, Robins-Browne RM, Strugnell RA, Korotkov KV, Lithgow T. 2013. Assembly of the type II secretion system such as found in Vibrio cholerae depends on the novel pilotin AspS. PLoS Pathog 9:e1003117. http://dx.doi.org/10.1371/journal.ppat.1003117. [PubMed]
115. Hu J, Worrall LJ, Hong C, Vuckovic M, Atkinson CE, Caveney N, Yu Z, Strynadka NCJ. 2018. Cryo-EM analysis of the T3S injectisome reveals the structure of the needle and open secretin. Nat Commun 9:3840. http://dx.doi.org/10.1038/s41467-018-06298-8. [PubMed]
116. Gu S, Rehman S, Wang X, Shevchik VE, Pickersgill RW. 2012. Structural and functional insights into the pilotin-secretin complex of the type II secretion system. PLoS Pathog 8:e1002531. http://dx.doi.org/10.1371/journal.ppat.1002531. [PubMed]
117. Strozen TG, Li G, Howard SP. 2012. YghG (GspSβ) is a novel pilot protein required for localization of the GspSβ type II secretion system secretin of enterotoxigenic Escherichia coli. Infect Immun 80:2608–2622. http://dx.doi.org/10.1128/IAI.06394-11. [PubMed]
118. Collin S, Guilvout I, Nickerson NN, Pugsley AP. 2011. Sorting of an integral outer membrane protein via the lipoprotein-specific Lol pathway and a dedicated lipoprotein pilotin. Mol Microbiol 80:655–665. http://dx.doi.org/10.1111/j.1365-2958.2011.07596.x. [PubMed]
119. Collin S, Guilvout I, Chami M, Pugsley AP. 2007. YaeT-independent multimerization and outer membrane association of secretin PulD. Mol Microbiol 64:1350–1357. http://dx.doi.org/10.1111/j.1365-2958.2007.05743.x. [PubMed]
120. Dunstan RA, Hay ID, Wilksch JJ, Schittenhelm RB, Purcell AW, Clark J, Costin A, Ramm G, Strugnell RA, Lithgow T. 2015. Assembly of the secretion pores GspD, Wza and CsgG into bacterial outer membranes does not require the Omp85 proteins BamA or TamA. Mol Microbiol 97:616–629. http://dx.doi.org/10.1111/mmi.13055. [PubMed]
121. Guilvout I, Brier S, Chami M, Hourdel V, Francetic O, Pugsley AP, Chamot-Rooke J, Huysmans GH. 2017. Prepore stability controls productive folding of the BAM-independent multimeric outer membrane secretin PulD. J Biol Chem 292:328–338. http://dx.doi.org/10.1074/jbc.M116.759498. [PubMed]
122. Korotkov KV, Gray MD, Kreger A, Turley S, Sandkvist M, Hol WGJ. 2009. Calcium is essential for the major pseudopilin in the type 2 secretion system. J Biol Chem 284:25466–25470. http://dx.doi.org/10.1074/jbc.C109.037655. [PubMed]
123. Cisneros DA, Bond PJ, Pugsley AP, Campos M, Francetic O. 2012. Minor pseudopilin self-assembly primes type II secretion pseudopilus elongation. EMBO J 31:1041–1053. http://dx.doi.org/10.1038/emboj.2011.454. [PubMed]
124. Reindl S, Ghosh A, Williams GJ, Lassak K, Neiner T, Henche AL, Albers SV, Tainer JA. 2013. Insights into FlaI functions in archaeal motor assembly and motility from structures, conformations, and genetics. Mol Cell 49:1069–1082. http://dx.doi.org/10.1016/j.molcel.2013.01.014. [PubMed]
125. Mancl JM, Black WP, Robinson H, Yang Z, Schubot FD. 2016. Crystal structure of a type IV pilus assembly ATPase: insights into the molecular mechanism of PilB from Thermus thermophilus. Structure 24:1886–1897. http://dx.doi.org/10.1016/j.str.2016.08.010. [PubMed]
126. McCallum M, Tammam S, Khan A, Burrows LL, Howell PL. 2017. The molecular mechanism of the type IVa pilus motors. Nat Commun 8:15091. http://dx.doi.org/10.1038/ncomms15091. [PubMed]
127. Gray MD, Bagdasarian M, Hol WGJ, Sandkvist M. 2011. In vivo cross-linking of EpsG to EpsL suggests a role for EpsL as an ATPase-pseudopilin coupling protein in the type II secretion system of Vibrio cholerae. Mol Microbiol 79:786–798. http://dx.doi.org/10.1111/j.1365-2958.2010.07487.x. [PubMed]
128. Nivaskumar M, Santos-Moreno J, Malosse C, Nadeau N, Chamot-Rooke J, Tran Van Nhieu G, Francetic O. 2016. Pseudopilin residue E5 is essential for recruitment by the type 2 secretion system assembly platform. Mol Microbiol 101:924–941. http://dx.doi.org/10.1111/mmi.13432. [PubMed]
129. Shevchik VE, Robert-Baudouy J, Condemine G. 1997. Specific interaction between OutD, an Erwinia chrysanthemi outer membrane protein of the general secretory pathway, and secreted proteins. EMBO J 16:3007–3016. http://dx.doi.org/10.1093/emboj/16.11.3007. [PubMed]
130. Bouley J, Condemine G, Shevchik VE. 2001. The PDZ domain of OutC and the N-terminal region of OutD determine the secretion specificity of the type II out pathway of Erwinia chrysanthemi. J Mol Biol 308:205–219. http://dx.doi.org/10.1006/jmbi.2001.4594. [PubMed]
131. Douzi B, Ball G, Cambillau C, Tegoni M, Voulhoux R. 2011. Deciphering the Xcp Pseudomonas aeruginosa type II secretion machinery through multiple interactions with substrates. J Biol Chem 286:40792–40801. http://dx.doi.org/10.1074/jbc.M111.294843. [PubMed]
132. Reichow SL, Korotkov KV, Gonen M, Sun J, Delarosa JR, Hol WGJ, Gonen T. 2011. The binding of cholera toxin to the periplasmic vestibule of the type II secretion channel. Channels (Austin) 5:215–218. http://dx.doi.org/10.4161/chan.5.3.15268.
133. Pineau C, Guschinskaya N, Robert X, Gouet P, Ballut L, Shevchik VE. 2014. Substrate recognition by the bacterial type II secretion system: more than a simple interaction. Mol Microbiol 94:126–140. http://dx.doi.org/10.1111/mmi.12744. [PubMed]
134. Michel-Souzy S, Douzi B, Cadoret F, Raynaud C, Quinton L, Ball G, Voulhoux R. 2018. Direct interactions between the secreted effector and the T2SS components GspL and GspM reveal a new effector-sensing step during type 2 secretion. J Biol Chem 293:19441–19450. http://dx.doi.org/10.1074/jbc.RA117.001127. [PubMed]
135. Nunn D. 1999. Bacterial type II protein export and pilus biogenesis: more than just homologies? Trends Cell Biol 9:402–408. http://dx.doi.org/10.1016/S0962-8924(99)01634-7.
136. Forest KT. 2008. The type II secretion arrowhead: the structure of GspI-GspJ-GspK. Nat Struct Mol Biol 15:428–430. http://dx.doi.org/10.1038/nsmb0508-428. [PubMed]
137. Nivaskumar M, Bouvier G, Campos M, Nadeau N, Yu X, Egelman EH, Nilges M, Francetic O. 2014. Distinct docking and stabilization steps of the pseudopilus conformational transition path suggest rotational assembly of type IV pilus-like fibers. Structure 22:685–696. http://dx.doi.org/10.1016/j.str.2014.03.001. [PubMed]
138. Nivaskumar M, Francetic O. 2014. Type II secretion system: a magic beanstalk or a protein escalator. Biochim Biophys Acta 1843:1568–1577. http://dx.doi.org/10.1016/j.bbamcr.2013.12.020. [PubMed]
139. O’Neal CJ, Amaya EI, Jobling MG, Holmes RK, Hol WGJ. 2004. Crystal structures of an intrinsically active cholera toxin mutant yield insight into the toxin activation mechanism. Biochemistry 43:3772–3782. http://dx.doi.org/10.1021/bi0360152. [PubMed]
140. Wedekind JE, Trame CB, Dorywalska M, Koehl P, Raschke TM, McKee M, FitzGerald D, Collier RJ, McKay DB. 2001. Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity. J Mol Biol 314:823–837. http://dx.doi.org/10.1006/jmbi.2001.5195. [PubMed]
141. Yoder MD, Jurnak F. 1995. Protein motifs. 3. The parallel beta helix and other coiled folds. FASEB J 9:335–342. http://dx.doi.org/10.1096/fasebj.9.5.7896002. [PubMed]
142. Yu AC, Worrall LJ, Strynadka NC. 2012. Structural insight into the bacterial mucinase StcE essential to adhesion and immune evasion during enterohemorrhagic E. coli infection. Structure 20:707–717. http://dx.doi.org/10.1016/j.str.2012.02.015. [PubMed]
143. Giglio KM, Fong JC, Yildiz FH, Sondermann H. 2013. Structural basis for biofilm formation via the Vibrio cholerae matrix protein RbmA. J Bacteriol 195:3277–3286. http://dx.doi.org/10.1128/JB.00374-13. [PubMed]
144. Maestre-Reyna M, Wu WJ, Wang AH. 2013. Structural insights into RbmA, a biofilm scaffolding protein of V. cholerae. PLoS One 8:e82458. http://dx.doi.org/10.1371/journal.pone.0082458. [PubMed]
145. Rule CS, Patrick M, Camberg JL, Maricic N, Hol WGJ, Sandkvist M. 2016. Zinc coordination is essential for the function and activity of the type II secretion ATPase EpsE. Microbiologyopen 5:870–882. http://dx.doi.org/10.1002/mbo3.376. [PubMed]
146. Fulara A, Vandenberghe I, Read RJ, Devreese B, Savvides SN. 2018. Structure and oligomerization of the periplasmic domain of GspL from the type II secretion system of Pseudomonas aeruginosa. Sci Rep 8:16760. http://dx.doi.org/10.1038/s41598-018-34956-w. [PubMed]
147. Zhang Y, Faucher F, Zhang W, Wang S, Neville N, Poole K, Zheng J, Jia Z. 2018. Structure-guided disruption of the pseudopilus tip complex inhibits the type II secretion in Pseudomonas aeruginosa. PLoS Pathog 14:e1007343. http://dx.doi.org/10.1371/journal.ppat.1007343. [PubMed]
148. Korotkov KV, Delarosa JR, Hol WGJ. 2013. A dodecameric ring-like structure of the N0 domain of the type II secretin from enterotoxigenic Escherichia coli. J Struct Biol 183:354–362. http://dx.doi.org/10.1016/j.jsb.2013.06.013. [PubMed]
149. Wretlind B, Pavlovskis OR. 1984. Genetic mapping and characterization of Pseudomonas aeruginosa mutants defective in the formation of extracellular proteins. J Bacteriol 158:801–808. [PubMed]
150. Bo JN, Howard SP. 1991. Mutagenesis and isolation of Aeromonas hydrophila genes which are required for extracellular secretion. J Bacteriol 173:1241–1249. http://dx.doi.org/10.1128/jb.173.3.1241-1249.1991.
151. Paranjpye RN, Lara JC, Pepe JC, Pepe CM, Strom MS. 1998. The type IV leader peptidase/N-methyltransferase of Vibrio vulnificus controls factors required for adherence to HEp-2 cells and virulence in iron-overloaded mice. Infect Immun 66:5659–5668. [PubMed]
152. Sikora AE, Zielke RA, Lawrence DA, Andrews PC, Sandkvist M. 2011. Proteomic analysis of the Vibrio cholerae type II secretome reveals new proteins, including three related serine proteases. J Biol Chem 286:16555–16566. http://dx.doi.org/10.1074/jbc.M110.211078. [PubMed]
153. Szabady RL, Yanta JH, Halladin DK, Schofield MJ, Welch RA. 2011. TagA is a secreted protease of Vibrio cholerae that specifically cleaves mucin glycoproteins. Microbiology 157:516–525. http://dx.doi.org/10.1099/mic.0.044529-0. [PubMed]
154. Golovkine G, Faudry E, Bouillot S, Voulhoux R, Attrée I, Huber P. 2014. VE-cadherin cleavage by LasB protease from Pseudomonas aeruginosa facilitates type III secretion system toxicity in endothelial cells. PLoS Pathog 10:e1003939. http://dx.doi.org/10.1371/journal.ppat.1003939. [PubMed]
155. DuMont AL, Cianciotto NP. 2017. Stenotrophomonas maltophilia serine protease StmPr1 induces matrilysis, anoikis, and protease-activated receptor 2 activation in human lung epithelial cells. Infect Immun 85:e00544-17. http://dx.doi.org/10.1128/IAI.00544-17. [PubMed]
156. Truchan HK, Christman HD, White RC, Rutledge NS, Cianciotto NP. 2017. Type II secretion substrates of Legionella pneumophila translocate out of the pathogen-occupied vacuole via a semipermeable membrane. mBio 8:e00870-17. http://dx.doi.org/10.1128/mBio.00870-17. [PubMed]
157. Jha G, Rajeshwari R, Sonti RV. 2005. Bacterial type two secretion system secreted proteins: double-edged swords for plant pathogens. Mol Plant Microbe Interact 18:891–898. http://dx.doi.org/10.1094/MPMI-18-0891. [PubMed]
158. Nascimento R, Gouran H, Chakraborty S, Gillespie HW, Almeida-Souza HO, Tu A, Rao BJ, Feldstein PA, Bruening G, Goulart LR, Dandekar AM. 2016. The type II secreted lipase/esterase LesA is a key virulence factor required for Xylella fastidiosa pathogenesis in grapevines. Sci Rep 6:18598. http://dx.doi.org/10.1038/srep18598. [PubMed]
159. Overbye LJ, Sandkvist M, Bagdasarian M. 1993. Genes required for extracellular secretion of enterotoxin are clustered in Vibrio cholerae. Gene 132:101–106. http://dx.doi.org/10.1016/0378-1119(93)90520-D.
160. Francetic O, Belin D, Badaut C, Pugsley AP. 2000. Expression of the endogenous type II secretion pathway in Escherichia coli leads to chitinase secretion. EMBO J 19:6697–6703. http://dx.doi.org/10.1093/emboj/19.24.6697. [PubMed]
161. Aragon V, Kurtz S, Cianciotto NP. 2001. Legionella pneumophila major acid phosphatase and its role in intracellular infection. Infect Immun 69:177–185. http://dx.doi.org/10.1128/IAI.69.1.177-185.2001. [PubMed]
162. Ball G, Durand E, Lazdunski A, Filloux A. 2002. A novel type II secretion system in Pseudomonas aeruginosa. Mol Microbiol 43:475–485. http://dx.doi.org/10.1046/j.1365-2958.2002.02759.x. [PubMed]
163. Putker F, Tommassen-van Boxtel R, Stork M, Rodríguez-Herva JJ, Koster M, Tommassen J. 2013. The type II secretion system (Xcp) of Pseudomonas putida is active and involved in the secretion of phosphatases. Environ Microbiol 15:2658–2671. [PubMed]
164. Rossier O, Dao J, Cianciotto NP. 2009. A type II secreted RNase of Legionella pneumophila facilitates optimal intracellular infection of Hartmannella vermiformis. Microbiology 155:882–890. http://dx.doi.org/10.1099/mic.0.023218-0. [PubMed]
165. Mulcahy H, Charron-Mazenod L, Lewenza S. 2010. Pseudomonas aeruginosa produces an extracellular deoxyribonuclease that is required for utilization of DNA as a nutrient source. Environ Microbiol 12:1621–1629. [PubMed]
166. DiChristina TJ, Moore CM, Haller CA. 2002. Dissimilatory Fe(III) and Mn(IV) reduction by Shewanella putrefaciens requires ferE, a homolog of the pulE ( gspE) type II protein secretion gene. J Bacteriol 184:142–151. http://dx.doi.org/10.1128/JB.184.1.142-151.2002. [PubMed]
167. Shi L, Deng S, Marshall MJ, Wang Z, Kennedy DW, Dohnalkova AC, Mottaz HM, Hill EA, Gorby YA, Beliaev AS, Richardson DJ, Zachara JM, Fredrickson JK. 2008. Direct involvement of type II secretion system in extracellular translocation of Shewanella oneidensis outer membrane cytochromes MtrC and OmcA. J Bacteriol 190:5512–5516. http://dx.doi.org/10.1128/JB.00514-08. [PubMed]
168. Kirn TJ, Jude BA, Taylor RK. 2005. A colonization factor links Vibrio cholerae environmental survival and human infection. Nature 438:863–866. http://dx.doi.org/10.1038/nature04249. [PubMed]
169. Cadoret F, Ball G, Douzi B, Voulhoux R. 2014. Txc, a new type II secretion system of Pseudomonas aeruginosa strain PA7, is regulated by the TtsS/TtsR two-component system and directs specific secretion of the CbpE chitin-binding protein. J Bacteriol 196:2376–2386. http://dx.doi.org/10.1128/JB.01563-14. [PubMed]
170. journal-id:
Loading

Article metrics loading...

/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0034-2018
2019-02-15
2019-08-25

Abstract:

The type II secretion system (T2SS) delivers toxins and a range of hydrolytic enzymes, including proteases, lipases, and carbohydrate-active enzymes, to the cell surface or extracellular space of Gram-negative bacteria. Its contribution to survival of both extracellular and intracellular pathogens as well as environmental species of proteobacteria is evident. This dynamic, multicomponent machinery spans the entire cell envelope and consists of a cytoplasmic ATPase, several inner membrane proteins, a periplasmic pseudopilus, and a secretin pore embedded in the outer membrane. Despite the -envelope configuration of the T2S nanomachine, proteins to be secreted engage with the system first once they enter the periplasmic compartment via the Sec or TAT export system. Thus, the T2SS is specifically dedicated to their outer membrane translocation. The many sequence and structural similarities between the T2SS and type IV pili suggest a common origin and argue for a pilus-mediated mechanism of secretion. This minireview describes the structures, functions, and interactions of the individual T2SS components and the general architecture of the assembled T2SS machinery and briefly summarizes the transport and function of a growing list of T2SS exoproteins. Recent advances in cryo-electron microscopy, which have led to an increased understanding of the structure-function relationship of the secretin channel and the pseudopilus, are emphasized.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Comment has been disabled for this content
Submit comment
Close
Comment moderation successfully completed

Figures

Image of Figure 1
Figure 1

A schematic diagram of topology and location of the conserved core components of the T2SS. The accessory components GspN, GspA, and GspB are not shown. A selection of the T2SS substrates of variable functions. Protein toxins include AB cholera toxin ( 139 ) and exotoxin A ( 140 ). Hydrolytic enzymes include VesB ( 68 ), lipase in complex with chaperone (shown in purple) ( 71 ), pullulanase ( 77 ), pectate lyase C ( 141 ), EHEC metalloprotease StcE ( 142 ), and aminopeptidase LapA ( 91 ). biofilm matrix protein RbmA is a scaffolding protein ( 143 , 144 ).

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

The ATPase is hexameric GspE with C6 and C2 symmetries ( 20 ). A close-up view shows the Zn binding site, which is required for the function of GspE ( 14 , 145 ). Inner membrane components include the cytoplasmic domain of GspF ( 19 ), cytoplasmic domain of GspL in complex with N1 domain of GspE ( 16 ), periplasmic domain of GspL ( 26 ), periplasmic domain of GspM ( 25 ), the homology region (HR) domain of ETEC GspC ( 32 ), and the PDZ domain of GspC ( 29 ). The structure of periplasmic domain of GspL (XcpY) has been recently published ( 146 ). Regarding pseudopilus components, in the GspG pseudopilus model based on the cryo-EM reconstruction ( 50 ), a close-up view shows the Ca binding site of GspG, minor pseudopilin GspH ( 47 ), and the trimeric complex of ETEC GspK-GspI-GspJ ( 48 ), and a close-up view shows a double-Ca binding site of GspK. The structure of a homologous XcpX-XcpV-XcpW complex from has been recently reported ( 147 ).

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

The side and top views of ETEC GspD-AspS complex ( 37 ), EPEC GspD ( 36 ), K-12 GspD ( 34 ), and GspD ( 35 ). A single secretin protomer is highlighted, with N1, N2, and N3 domains in shades of blue, the secretin domain in green, and the S domain in magenta. Several AspS protomers (brown) were omitted to clearly show the location of the S domain. The cap subdomain in the -type secretins is highlighted in orange. The N0 domains (purple) were not resolved in the available cryo-EM reconstructions due to flexibility. Instead, its approximate location is indicated ( 148 ). Note that the N1-N2 domains of EPEC GspD ( 36 ) and the N1 domain of GspD ( 35 ) have been placed as rigid fit models. Structures of pilotins in complex with the secretin S domains (magenta). Structures of -type ETEC AspS ( 37 ) and -type GspS ( 116 ) are shown.

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table
TABLE 1

Examples of T2SS substrates

Citation: Korotkov K, Sandkvist M. 2019. Architecture, Function, and Substrates of the Type II Secretion System, EcoSal Plus 2019; doi:10.1128/ecosalplus.ESP-0034-2018

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error