Type VI secretion system: Secretion by a contractile nanomachine

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 370, Issue 1679, 2015, Pages

  Basler, Marek ^a  

^a UNIVERSITY OF BASEL   (Switzerland)

Author keywords

Contractile phage tail; Dynamics; Effectors; Energetics; Structure; Type VI secretion system

Indexed keywords

BACTERIUM; CELLS AND CELL COMPONENTS; ENERGY EFFICIENCY; EUKARYOTE; MACHINERY; PATHOGENICITY; POLYMERIZATION; SECRETION;

BACTERIA (MICROORGANISMS); EUKARYOTA;

BACTERIAL PROTEIN; NANOMATERIAL; TYPE VI SECRETION SYSTEM;

BIOLOGICAL MODEL; CHEMISTRY; GRAM NEGATIVE BACTERIUM; PHYSIOLOGY; PROTEIN MULTIMERIZATION; TYPE VI SECRETION SYSTEM;

BACTERIAL PROTEINS; GRAM-NEGATIVE BACTERIA; MODELS, BIOLOGICAL; NANOSTRUCTURES; PROTEIN MULTIMERIZATION; TYPE VI SECRETION SYSTEMS;

EID: 84941710294     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2015.0021     Document Type: Review

References (125)

1. Costa TRD, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G. 2015 Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat. Rev. Microbiol. 13, 343-359. (doi:10.1038/nrmicro3456)
2. Pukatzki S, Ma AT, Sturtevant D, Krastins B, Sarracino D, Nelson WC, Heidelberg JF, Mekalanos JJ. 2006 Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc. Natl Acad. Sci. USA 103, 1528-1533. (doi:10.1073/pnas. 0510322103)
3. Das S, Chaudhuri K. 2003 Identification of a unique IAHP (IcmF associated homologous proteins) cluster in Vibrio cholerae and other proteobacteria through in silico analysis. In Silico Biol. 3, 287-300.
4. Williams SG, Varcoe LT, Attridge SR, Manning PA. 1996 Vibrio cholerae Hcp, a secreted protein coregulated with HlyA. Infect Immun. 64, 283-289.
5. Sheahan K-L, Cordero CL, Satchell KJF. 2004 Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin. Proc. Natl Acad. Sci. USA 101, 9798-9803. (doi:10.1073/pnas.0401104101)
6. Mougous JD et al. 2006 A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526-1530. (doi:10.1126/science.1128393)
7. Zheng J, Leung KY. 2007 Dissection of a type VI secretion system in Edwardsiella tarda. Mol. Microbiol. 66, 1192-1206. (doi:10.1111/j.13652958.2007.05993.x)
8. Schlieker C, Zentgraf H, Dersch P, Mogk A. 2005 ClpV, a unique Hsp100/Clp member of pathogenic proteobacteria. Biol. Chem. 386, 1115-1127. (doi:10.1515/BC.2005.128)
9. Filloux A, Hachani A, Bleves S. 2008 The bacterial type VI secretion machine: yet another player for protein transport across membranes. Microbiology 154, 1570-1583. (doi:10.1099/mic.0.2008/ 016840-0)
10. Bingle LE, Bailey CM, Pallen MJ. 2008 Type VI secretion: a beginner’s guide. Curr. Opin. Microbiol. 11, 3-8. (doi:10.1016/j.mib.2008.01.006)
11. Coulthurst SJ. 2013 The Type VI secretion system - a widespread and versatile cell targeting system. Res. Microbiol. 164, 640-654. (doi:10.1016/j. resmic.2013.03.017)
12. Ho BT, Dong TG, Mekalanos JJ. 2014 A view to a kill: the bacterial type VI secretion system. Cell Host Microbe 15, 9-21. (doi:10.1016/j.chom. 2013.11.008)
13. Kapitein N, Mogk A. 2013 Deadly syringes: type VI secretion system activities in pathogenicity and interbacterial competition. Curr. Opin. Microbiol. 16, 52-58. (doi:10.1016/j.mib.2012.11.009)
14. Durand E, Cambillau C, Cascales E, Journet L. 2014 VgrG, Tae, Tle, and beyond: the versatile arsenal of Type VI secretion effectors. Trends Microbiol. 22, 498-507. (doi:10.1016/j.tim.2014.06.004)
15. Russell AB, Peterson SB, Mougous JD. 2014 Type VI secretion system effectors: poisons with a purpose. Nat. Rev. Microbiol. 12, 137-148. (doi:10.1038/ nrmicro3185)
16. Cascales E, Cambillau C. 2012 Structural biology of type VI secretion systems. Phil. Trans. R. Soc. B 367, 1102-1111. (doi:10.1098/rstb.2011.0209)
17. Silverman JM, Brunet YR, Cascales E, Mougous JD. 2012 Structure and regulation of the type VI secretion system. Annu. Rev. Microbiol. 66, 453- 472. (doi:10.1146/annurev-micro-121809-151619)
18. Zoued A, Brunet YR, Durand E, Aschtgen M-S, Logger L, Douzi B, Journet L, Cambillau C, Cascales E. 2014 Architecture and assembly of the Type VI secretion system. Biochim. Biophys. Acta 1843, 1664-1673. (doi:10.1016/j.bbamcr.2014.03.018)
19. Leiman PG et al. 2009 Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin. Proc. Natl Acad. Sci. USA 106, 4154-4159. (doi:10.1073/pnas. 0813360106)
20. Pukatzki S, Ma AT, Revel AT, Sturtevant D, Mekalanos JJ. 2007 Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. Proc. Natl Acad. Sci. USA 104, 15 508-15 513. (doi:10.1073/ pnas.0706532104)
21. Pell LG, Kanelis V, Donaldson LW, Howell PL, Davidson AR. 2009 The phage lambda major tail protein structure reveals a common evolution for long-tailed phages and the type VI bacterial secretion system. Proc. Natl Acad. Sci. USA 106, 4160-4165. (doi:10.1073/pnas.0900044106)
22. Lossi NS, Dajani R, Freemont P, Filloux A. 2011 Structure-function analysis of HsiF, a gp25-like component of the type VI secretion system, in Pseudomonas aeruginosa. Microbiology 157, 3292-3305. (doi:10.1099/mic.0.051987-0)
23. Bönemann G, Pietrosiuk A, Diemand A, Zentgraf H, Mogk A. 2009 Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion. EMBO J. 28, 315-325. (doi:10. 1038/emboj.2008.269)
24. Leiman PG, Shneider MM. 2012 Contractile tail machines of bacteriophages. Adv. Exp. Med. Biol. 726, 93-114. (doi:10.1007/978-1-46140980-9_5)
25. Leiman PG, Arisaka F, van Raaij MJ, Kostyuchenko VA, Aksyuk AA, Kanamaru S, Rossmann MG. 2010 Morphogenesis of the T4 tail and tail fibers. Virol. J. 7, 355. (doi:10.1186/1743-422X-7-355)
26. Basler M, Pilhofer M, Henderson GP, Jensen GJ, Mekalanos JJ. 2012 Type VI secretion requires a dynamic contractile phage tail-like structure. Nature 483, 182-186. (doi:10.1038/nature10846)
27. Li Z, Jensen GJ. 2009 Electron cryotomography: a new view into microbial ultrastructure. Curr. Opin. Microbiol. 12, 333-340. (doi:10.1016/j.mib.2009.03.007)
28. Pilhofer M, Ladinsky MS, McDowall AW, Jensen GJ. 2010 Bacterial TEM: new insights from cryo microscopy. Methods Cell Biol. 96, 21-45. (doi:10. 1016/S0091-679X(10)96002-0)
29. Basler M, Mekalanos JJ. 2012 Type 6 secretion dynamics within and between bacterial cells. Science 337, 815. (doi:10.1126/science.1222901)
30. Brunet YR, Espinosa L, Harchouni S, Mignot T, Cascales E. 2013 Imaging type VI secretionmediated bacterial killing. Cell Rep. 3, 36-41. (doi:10.1016/j.celrep.2012.11.027)
31. Kapitein N, Bonemann G, Pietrosiuk A, Seyffer F, Hausser I, Locker JK, Mogk A. 2013 ClpV recycles VipA/VipB tubules and prevents non-productive tubule formation to ensure efficient type VI protein secretion. Mol. Microbiol. 87, 1013-1028. (doi:10. 1111/mmi.12147)
32. Aschtgen M-S, Bernard CS, De Bentzmann S, Lloubès R, Cascales E. 2008 SciN is an outer membrane lipoprotein required for type VI secretion in enteroaggregative Escherichia coli. J. Bacteriol. 190, 7523-7531. (doi:10.1128/JB.00945-08)
33. Aschtgen M-S, Gavioli M, Dessen A, Lloubès R, Cascales E. 2010 The SciZ protein anchors the enteroaggregative Escherichia coli Type VI secretion system to the cell wall. Mol. Microbiol. 75, 886-899. (doi:10.1111/j.1365-2958.2009. 07028.x)
34. Durand E et al. 2015 Biogenesis and structure of a type VI secretion membrane core complex. Nature 523, 555-560. (doi:10.1038/nature14667)
35. Felisberto-Rodrigues C et al. 2011 Towards a structural comprehension of bacterial type VI secretion systems: characterization of the TssJ-TssM complex of an Escherichia coli pathovar. PLoS Pathog. 7, e1002386. (doi:10.1371/journal.ppat.1002386)
36. Ma L-S, Lin J-S, Lai E-M. 2009 An IcmF family protein, ImpLM, is an integral inner membrane protein interacting with ImpKL, and its Walker A motif is required for type VI secretion systemmediated Hcp secretion in Agrobacterium tumefaciens. J. Bacteriol. 191, 4316-4329. (doi:10. 1128/JB.00029-09)
37. Ma L-S, Narberhaus F, Lai E-M. 2012 IcmF family protein TssM exhibits ATPase activity and energizes type VI secretion. J. Biol. Chem. 287, 15 610- 15 621. (doi:10.1074/jbc.M111.301630)
38. Aschtgen M-S, Thomas MS, Cascales E. 2010 Anchoring the type VI secretion system to the peptidoglycan: TssL, TagL, TagP…what else? Virulence 1, 535-540. (doi:10.4161/viru.1.6.13732)
39. Chang JH, Kim Y-G. 2015 Crystal structure of the bacterial type VI secretion system component TssL from Vibrio cholerae. J. Microbiol. 53, 32-37. (doi:10.1007/s12275-015-4539-0)
40. Durand E, Zoued A, Spinelli S, Watson PJH, Aschtgen M-S, Journet L, Cambillau C, Cascales E. 2012 Structural characterization and oligomerization of the TssL protein, a component shared by bacterial type VI and type IVb secretion systems. J. Biol. Chem. 287, 14 157-14 168. (doi:10.1074/ jbc.M111.338731)
41. Robb CS, Nano FE, Boraston AB. 2012 The structure of the conserved type six secretion protein TssL (DotU) from Francisella novicida. J. Mol. Biol. 419, 277-283. (doi:10.1016/j.jmb.2012.04.003)
42. Rao VA, Shepherd SM, English G, Coulthurst SJ, Hunter WN. 2011 The structure of Serratia marcescens Lip, a membrane-bound component of the type VI secretion system. Acta Crystallogr. D Biol. Crystallogr. 67, 1065-1072. (doi:10.1107/ S0907444911046300)
43. Robb CS, Assmus M, Nano FE, Boraston AB. 2013 Structure of the T6SS lipoprotein TssJ1 from Pseudomonas aeruginosa. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69, 607-610. (doi:10. 1107/S1744309113012220)
44. Zoued A, Durand E, Bebeacua C, Brunet YR, Douzi B, Cambillau C, Cascales E, Journet L. 2013 TssK is a trimeric cytoplasmic protein interacting with components of both phage-like and membrane anchoring complexes of the type VI secretion system. J. Biol. Chem. 288, 27 031-27 041. (doi:10. 1074/jbc.M113.499772)
45. English G, Byron O, Cianfanelli FR, Prescott AR, Coulthurst SJ. 2014 Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK-TssFG subcomplex. Biochem. J. 461, 291-304. (doi:10.1042/BJ20131426)
46. Ge P, Scholl D, Leiman PG, Yu X, Miller JF, Zhou ZH. 2015 Atomic structures of a bactericidal contractile nanotube in its pre- and postcontraction states. Nat. Struct. Mol. Biol. 22, 377-382. (doi:10.1038/nsmb.2995)
47. Kudryashev M et al. 2015 Structure of the type VI secretion system contractile sheath. Cell 160, 952-962. (doi:10.1016/j.cell.2015.01.037)
48. Bernard CS, Brunet YR, Gueguen E, Cascales E. 2010 Nooks and crannies in type VI secretion regulation. J. Bacteriol. 192, 3850-3860. (doi:10.1128/JB. 00370-10)
49. Miyata ST, Bachmann V, Pukatzki S. 2013 Type VI secretion system regulation as a consequence of evolutionary pressure. J. Med. Microbiol. 62, 663-676. (doi:10.1099/jmm.0.053983-0)
50. Mougous JD, Gifford CA, Ramsdell TL, Mekalanos JJ. 2007 Threonine phosphorylation post-translationally regulates protein secretion in Pseudomonas aeruginosa. Nat. Cell Biol. 9, 797-803. (doi:10. 1038/ncb1605)
51. Fritsch MJ, Trunk K, Diniz JA, Guo M, Trost M, Coulthurst SJ. 2013 Proteomic identification of novel secreted antibacterial toxins of the Serratia marcescens type VI secretion system. Mol. Cell Proteomics 12, 2735-2749. (doi:10.1074/mcp. M113.030502)
52. Lin J-S, Ma L-S, Lai E-M. 2013 Systematic dissection of the agrobacterium type VI secretion system reveals machinery and secreted components for subcomplex formation. PLoS ONE 8, e67647. (doi:10.1371/journal.pone.0067647)
53. Lin J-S, Wu H-H, Hsu P-H, Ma L-S, Pang Y-Y, Tsai M-D, Lai E-M. 2014 Fha interaction with phosphothreonine of TssL activates type VI secretion in Agrobacterium tumefaciens. PLoS Pathog. 10, e1003991. (doi:10.1371/journal.ppat. 1003991)
54. Hsu F, Schwarz S, Mougous JD. 2009 TagR promotes PpkA-catalysed type VI secretion activation in Pseudomonas aeruginosa. Mol. Microbiol. 72, 1111- 1125. (doi:10.1111/j.1365-2958.2009.06701.x)
55. Casabona MG et al. 2013 An ABC transporter and an outer membrane lipoprotein participate in posttranslational activation of type VI secretion in Pseudomonas aeruginosa. Environ. Microbiol. 15, 471-486. (doi:10.1111/j.1462-2920.2012.02816.x)
56. Silverman JM, Austin LS, Hsu F, Hicks KG, Hood RD, Mougous JD. 2011 Separate inputs modulate phosphorylation-dependent and -independent type VI secretion activation. Mol. Microbiol. 82, 1277- 1290. (doi:10.1111/j.1365-2958.2011.07889.x)
57. Basler M, Ho BT, Mekalanos JJ. 2013 Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152, 884-894. (doi:10.1016/j.cell.2013.01.042)
58. LeRoux M et al. 2012 Quantitative single-cell characterization of bacterial interactions reveals type VI secretion is a double-edged sword. Proc. Natl Acad. Sci. USA 109, 19 804-19 809. (doi:10.1073/ pnas.1213963109)
59. Ho BT, Basler M, Mekalanos JJ. 2013 Type 6 secretion system-mediated immunity to type 4 secretion system-mediated gene transfer. Science 342, 250-253. (doi:10.1126/science.1243745)
60. LeRoux M et al. 2015 Kin cell lysis is a danger signal that activates antibacterial pathways of Pseudomonas aeruginosa. Elife 4, e05701. (doi:10. 7554/eLife.05701)
61. Crowther RA, Lenk EV, Kikuchi Y, King J. 1977 Molecular reorganization in the hexagon to star transition of the baseplate of bacteriophage T4. J. Mol. Biol. 116, 489-523. (doi:10.1016/00222836(77)90081-X)
62. Kostyuchenko VA, Chipman PR, Leiman PG, Arisaka F, Mesyanzhinov VV, Rossmann MG. 2005 The tail structure of bacteriophage T4 and its mechanism of contraction. Nat. Struct. Mol. Biol. 12, 810-813. (doi:10.1038/nsmb975)
63. Leiman PG, Chipman PR, Kostyuchenko VA, Mesyanzhinov VV, Rossmann MG. 2004 Threedimensional rearrangement of proteins in the tail of bacteriophage T4 on infection of its host. Cell. 118, 419-429. (doi:10.1016/j.cell.2004.07.022)
64. Arisaka F, Tschopp J, van Driel R, Engel J. 1979 Reassembly of the bacteriophage T4 tail from the core-baseplate and the monomeric sheath protein P18: a co-operative association process. J. Mol. Biol. 132, 369-386. (doi:10.1016/0022-2836(79) 90266-3)
65. Arisaka F, Engel J, Klump H. 1981 Contraction and dissociation of the bacteriophage T4 tail sheath induced by heat and urea. Prog. Clin. Biol. Res. 64, 365-379.
66. Veesler D, Cambillau C. 2011 A common evolutionary origin for tailed-bacteriophage functional modules and bacterial machineries. Microbiol. Mol. Biol. Rev. 75, 423-433. (doi:10. 1128/MMBR.00014-11)
67. Shneider MM, Buth SA, Ho BT, Basler M, Mekalanos JJ, Leiman PG. 2013 PAAR-repeat proteins sharpen and diversify the type VI secretion system spike. Nature 500, 350-353. (doi:10.1038/nature12453)
68. Brunet YR, Henin J, Celia H, Cascales E. 2014 Type VI secretion and bacteriophage tail tubes share a common assembly pathway. EMBO Rep. 15, 315-321. (doi:10.1002/embr.201337936)
69. Ballister ER, Lai AH, Zuckermann RN, Cheng Y, Mougous JD. 2008 In vitro self-assembly of tailorable nanotubes from a simple protein building block. Proc. Natl Acad. Sci. USA 105, 3733-3738. (doi:10.1073/pnas.0712247105)
70. Douzi B, Spinelli S, Blangy S, Roussel A, Durand E, Brunet YR, Cascales E, Cambillau C. 2014 Crystal structure and self-interaction of the type VI secretion tail-tube protein from enteroaggregative Escherichia coli. PLoS ONE 9, e86918. (doi:10.1371/ journal.pone.0086918)
71. Tschopp J, Arisaka F, van Driel R, Engel J. 1979 Purification, characterization and reassembly of the bacteriophage T4D tail sheath protein P18. J. Mol. Biol. 128, 247-258. (doi:10.1016/0022-2836(79) 90128-1)
72. Jobichen C, Chakraborty S, Li M, Zheng J, Joseph L, Mok Y-K, Leung KY, Sivaraman J. 2010 Structural basis for the secretion of EvpC: a key type VI secretion system protein from Edwardsiella tarda. PLoS ONE 5, e12910. (doi:10.1371/journal.pone.0012910)
73. Moody MF. 1967 Structure of the sheath of bacteriophage T4. II. Rearrangement of the sheath subunits during contraction. J. Mol. Biol. 25, 201-208. (doi:10.1016/0022-2836(67)90137-4)
74. Moody MF. 1973 Sheath of bacteriophage T4. 3. Contraction mechanism deduced from partially contracted sheaths. J. Mol. Biol. 80, 613-635. (doi:10.1016/0022-2836(73)90200-3)
75. Aksyuk AA, Leiman PG, Kurochkina LP, Shneider MM, Kostyuchenko VA, Mesyanzhinov VV, Rossmann MG. 2009 The tail sheath structure of bacteriophage T4: a molecular machine for infecting bacteria. EMBO J. 28, 821-829. (doi:10.1038/emboj.2009.36)
76. Clemens DL, Ge P, Lee B-Y, Horwitz MA, Zhou ZH. 2015 Atomic structure of T6SS reveals interlaced array essential to function. Cell 160, 940-951. (doi:10.1016/j.cell.2015.02.005)
77. Tran QH, Unden G. 1998 Changes in the proton potential and the cellular energetics of Escherichia coli during growth by aerobic and anaerobic respiration or by fermentation. Eur. J. Biochem. 251, 538-543. (doi:10.1046/j.1432-1327.1998. 2510538.x)
78. Kenniston JA, Baker TA, Fernandez JM, Sauer RT. 2003 Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAAþ degradation machine. Cell 114, 511-520. (doi:10.1016/S0092-8674(03) 00612-3)
79. Gatsogiannis C, Lang AE, Meusch D, Pfaumann V, Hofnagel O, Benz R, Aktories K, Raunser S. 2013 A syringe-like injection mechanism in Photorhabdus luminescens toxins. Nature 495, 520-523. (doi:10. 1038/nature11987)
80. Meusch D, Gatsogiannis C, Efremov RG, Lang AE, Hofnagel O, Vetter IR, Aktories K, Raunser S. 2014 Mechanism of Tc toxin action revealed in molecular detail. Nature 508, 61-65. (doi:10.1038/ nature13015)
81. Visscher K, Schnitzer MJ, Block SM. 1999 Single kinesin molecules studied with a molecular force clamp. Nature 400, 184-189. (doi:10.1038/22146)
82. Zheng J, Ho B, Mekalanos JJ. 2011 Genetic analysis of anti-amoebae and anti-bacterial activities of the type VI secretion system in Vibrio cholerae. PLoS ONE 6, e23876. (doi:10.1371/journal. pone.0023876)
83. Pietrosiuk A, Lenherr ED, Falk S, Bönemann G, Kopp J, Zentgraf H, Sinning I, Mogk A. 2011 Molecular basis for the unique role of the AAAþ chaperone ClpV in type VI protein secretion. J. Biol. Chem. 286, 30 010-30 021. (doi:10.1074/jbc.M111.253377)
84. Kube S, Kapitein N, Zimniak T, Herzog F, Mogk A, Wendler P. 2014 Structure of the VipA/B type VI secretion complex suggests a contraction-statespecific recycling mechanism. Cell Rep. 8, 20-30. (doi:10.1016/j.celrep.2014.05.034)
85. Förster A, Planamente S, Manoli E, Lossi NS, Freemont PS, Filloux A. 2014 Coevolution of the ATPase ClpV, the sheath proteins TssB and TssC, and the accessory protein TagJ/HsiE1 distinguishes type VI secretion classes. J. Biol. Chem. 289, 33 032- 33 043. (doi:10.1074/jbc.M114.600510)
86. Lossi NS, Manoli E, Simpson P, Jones C, Hui K, Dajani R, Coulthurst SJ, Freemont P, Filloux A. 2012 The archetype Pseudomonas aeruginosa proteins TssB and TagJ form a novel subcomplex in the bacterial type VI secretion system. Mol. Microbiol. 86, 437-456. (doi:10.1111/j.1365-2958.2012.08204.x)
87. Murdoch SL, Trunk K, English G, Fritsch MJ, Pourkarimi E, Coulthurst SJ. 2011 The opportunistic pathogen Serratia marcescens utilizes type VI secretion to target bacterial competitors. J. Bacteriol. 193, 6057-6069. (doi:10.1128/JB.05671-11)
88. Silverman JM, Agnello DM, Zheng H, Andrews BT, Li M, Catalano CE, Gonen T, Mougous JD. 2013 Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates. Mol. Cell. 51, 584-593. (doi:10.1016/j. molcel.2013.07.025)
89. Hood RD et al. 2010 A type VI secretion system of Pseudomonas aeruginosa targets a toxin to bacteria. Cell Host Microbe 7, 25-37. (doi:10.1016/j.chom. 2009.12.007)
90. Russell AB et al. 2012 A widespread bacterial type VI secretion effector superfamily identified using a heuristic approach. Cell Host Microbe 11, 538-549. (doi:10.1016/j.chom.2012.04.007)
91. Salomon D, Kinch LN, Trudgian DC, Guo X, Klimko JA, Grishin NV, Mirzaei H, Orth K. 2014 Marker for type VI secretion system effectors. Proc. Natl Acad. Sci. USA 111, 9271-9276. (doi:10.1073/pnas. 1406110111)
92. Dong TG, Ho BT, Yoder-Himes DR, Mekalanos JJ. 2013 Identification of T6SS-dependent effector and immunity proteins by Tn-seq in Vibrio cholerae. Proc. Natl Acad. Sci. USA 110, 2623-2628. (doi:10. 1073/pnas.1222783110)
93. Whitney JC et al. 2014 Genetically distinct pathways guide effector export through the type VI secretion system. Mol. Microbiol. 92, 529-542. (doi:10.1111/ mmi.12571)
94. Zhang D, de Souza RF, Anantharaman V, Iyer LM, Aravind L. 2012 Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics. Biol. Direct 7, 18. (doi:10.1186/1745-6150-7-18)
95. Koskiniemi S, Lamoureux JG, Nikolakakis KC, t’Kint deRoodenbeke C, Kaplan MD, Low DA, Low DA, Hayes CS. 2013 Rhs proteins from diverse bacteria mediate intercellular competition. Proc. Natl Acad. Sci. USA 110, 7032-7037. (doi:10.1073/pnas. 1300627110)
96. Ma L-S, Hachani A, Lin J-S, Filloux A, Lai E-M. 2014 Agrobacterium tumefaciens deploys a superfamily of type VI secretion DNase effectors as weapons for interbacterial competition in planta. Cell Host Microbe 16, 94-104. (doi:10.1016/j.chom.2014.06.002)
97. Unterweger D, Miyata ST, Bachmann V, Brooks TM, Mullins T, Kostiuk B, Provenzano D, Pukatzki S. 2014 The Vibrio cholerae type VI secretion system employs diverse effector modules for intraspecific competition. Nat. Commun. 5, 3549. (doi:10.1038/ ncomms4549)
98. Jiang F, Waterfield NR, Yang J, Yang G, Jin Q. 2014 A Pseudomonas aeruginosa type VI secretion phospholipase D effector targets both prokaryotic and eukaryotic cells. Cell Host Microbe 15, 600-610. (doi:10.1016/j.chom.2014.04.010)
99. Russell AB, LeRoux M, Hathazi K, Agnello DM, Ishikawa T, Wiggins PA, Wai SN, Mougous JD. 2013 Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors. Nature 496, 508-512. (doi:10.1038/nature12074)
100. 2þ to combat multiple stresses and host immunity. PLoS Pathog. 11, e1005020. (doi:10. 1371/journal.ppat.1005020)
101. Schwarz S, Singh P, Robertson JD, LeRoux M, Skerrett SJ, Goodlett DR, West TE, Mougous JD. 2014 VgrG-5 is a Burkholderia type VI secretion system-exported protein required for multinucleated giant cell formation and virulence. Infect. Immun. 82, 1445-1452. (doi:10.1128/IAI.01368-13)
102. Toesca IJ, French CT, Miller JF. 2014 The Type VI secretion system spike protein VgrG mediates membrane fusion during intercellular spread by pseudomallei-group Burkholderia species. Infect. Immun. 82, 1436-1444. (doi:10.1128/IAI. 01367-13)
103. Suarez G, Sierra JC, Erova TE, Sha J, Horneman AJ, Chopra AK. 2010 A type VI secretion system effector protein, VgrG1, from Aeromonas hydrophila that induces host cell toxicity by ADP ribosylation of actin. J. Bacteriol. 192, 155-168. (doi:10.1128/JB. 01260-09)
104. Brooks TM, Unterweger D, Bachmann V, Kostiuk B, Pukatzki S. 2013 Lytic activity of the Vibrio cholerae type VI secretion toxin VgrG-3 is inhibited by the antitoxin TsaB. J. Biol. Chem. 288, 7618-7625. (doi:10.1074/jbc.M112.436725)
105. Liang X, Moore R, Wilton M, Wong MJQ, Lam L, Dong TG. 2015 Identification of divergent type VI secretion effectors using a conserved chaperone domain. Proc. Natl Acad. Sci. USA 112, 9106-9111. (doi:10.1073/pnas.1505317112)
106. Unterweger D, Kostiuk B, Ötjengerdes R, Wilton A, Diaz-Satizabal L, Pukatzki S. In press. Chimeric adaptor proteins translocate diverse type VI secretion system effectors in Vibrio cholerae. EMBO J. (doi:10.15252/embj.201591163)
107. Alcoforado Diniz J, Coulthurst SJ. 2015 Intraspecies competition in Serratia marcescens is mediated by type VI-secreted Rhs effectors and a conserved effector-associated accessory protein. J. Bacteriol. 197, 2350-2360. (doi:10.1128/JB.00199-15)
108. Hachani A, Allsopp LP, Oduko Y, Filloux A. 2014 The VgrG proteins are ‘à la carte’ delivery systems for bacterial type VI effectors. J. Biol. Chem. 289, 17 872-17 884. (doi:10.1074/jbc.M114.563429)
109. Wenren LM, Sullivan NL, Cardarelli L, Septer AN, Gibbs KA. 2013 Two independent pathways for selfrecognition in Proteus mirabilis are linked by type VI-dependent export. MBio 4, e00374. (doi:10.1128/ mBio.00374-13)
110. Osipiuk J, Xu X, Cui H, Savchenko A, Edwards A, Joachimiak A. 2011 Crystal structure of secretory protein Hcp3 from Pseudomonas aeruginosa. J. Struct. Funct. Genomics 12, 21-26. (doi:10.1007/ s10969-011-9107-1)
111. Ruiz FM, Santillana E, Spínola-Amilibia M, Torreira E, Culebras E, Romero A. 2015 Crystal structure of Hcp from Acinetobacter baumannii: a component of the type VI secretion system. PLoS ONE 10, e0129691. (doi:10.1371/journal.pone.0129691)
112. Chou S, Bui NK, Russell AB, Lexa KW, Gardiner TE, LeRoux M, Vollmer W, Mougous JD. 2012 Structure of a peptidoglycan amidase effector targeted to Gram-negative bacteria by the type VI secretion system. Cell Rep. 1, 656-664. (doi:10.1016/j.celrep. 2012.05.016)
113. Blondel CJ, Jiménez JC, Contreras I, Santiviago CA. 2009 Comparative genomic analysis uncovers 3 novel loci encoding type six secretion systems differentially distributed in Salmonella serotypes. BMC Genomics 10, 354. (doi:10.1186/1471-2164-10-354)
114. Browning C, Shneider MM, Bowman VD, Schwarzer D, Leiman PG. 2012 Phage pierces the host cell membrane with the iron-loaded spike. Structure 20, 326-339. (doi:10.1016/j.str.2011.12.009)
115. Kanamaru S, Leiman PG, Kostyuchenko VA, Chipman PR, Mesyanzhinov VV, Arisaka F, Rossmann MG. 2002 Structure of the cell-puncturing device of bacteriophage T4. Nature 415, 553-557. (doi:10. 1038/415553a)
116. Busby JN, Panjikar S, Landsberg MJ, Hurst MRH, Lott JS. 2013 The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device. Nature 501, 547-550. (doi:10.1038/nature12465)
117. Gebhart D et al. 2012 Novel high-molecular-weight, R-type bacteriocins of Clostridium difficile. J. Bacteriol. 194, 6240-6247. (doi:10.1128/JB. 01272-12)
118. Michel-Briand Y, Baysse C. 2002 The pyocins of Pseudomonas aeruginosa. Biochimie 84, 499-510. (doi:10.1016/S0300-9084(02)01422-0)
119. Nakayama K et al. 2000 The R-type pyocin of Pseudomonas aeruginosa is related to P2 phage, and the F-type is related to lambda phage. Mol. Microbiol. 38, 213-231. (doi:10.1046/j.1365-2958. 2000.02135.x)
120. Kageyama M, Ikeda K, Egami F. 1964 Studies of a pyocin. iii. Biological properties of the pyocin. J. Biochem. 55, 59-64.
121. Ritchie JM, Greenwich JL, Davis BM, Bronson RT, Gebhart D, Williams SR, Martin D, Scholl D, Waldor MK. 2011 An Escherichia coli O157-specific engineered pyocin prevents and ameliorates infection by E. coli O157:H7 in an animal model of diarrheal disease. Antimicrob. Agents Chemother. 55, 5469-5474. (doi:10.1128/AAC.05031-11)
122. Scholl D, Cooley M, Williams SR, Gebhart D, Martin D, Bates A, Mandrell R. 2009 An engineered R-type pyocin is a highly specific and sensitive bactericidal agent for the food-borne pathogen Escherichia coli O157:H7. Antimicrob. Agents Chemother. 53, 3074-3080. (doi:10.1128/AAC. 01660-08)
123. Heymann JB, Bartho JD, Rybakova D, Venugopal HP, Winkler DC, Sen A, Hurst MRH, Mitra AK. 2013 Three-dimensional structure of the toxin-delivery particle antifeeding prophage of Serratia entomophila. J. Biol. Chem. 288, 25 276-25 284. (doi:10.1074/jbc.M113.456145)
124. Shikuma NJ, Pilhofer M, Weiss GL, Hadfield MG, Jensen GJ, Newman DK. 2014 Marine tubeworm metamorphosis induced by arrays of bacterial phage tail-like structures. Science 343, 529-533. (doi:10.1126/science. 1246794)
125. Yang G, Dowling AJ, Gerike U, ffrench-Constant RH, Waterfield NR. 2006 Photorhabdus virulence cassettes confer injectable insecticidal activity against the wax moth. J. Bacteriol. 188, 2254-2261. (doi:10.1128/JB.188.6.22542261.2006)