The role of the Francisella tularensis pathogenicity island in type VI secretion, intracellular survival, and modulation of host cell signaling

Frontiers in Microbiology

Volumn 1, Issue DEC, 2010, Pages

  Bröms, Jeanette E ^a   Sjöstedt, Anders ^a   Lavander, Moa ^a  

^a UMEÅ UNIVERSITY   (Sweden)

Author keywords

FPI; Francisella tularensis; Intracellular growth; Phagosomal escape; T6SS

Indexed keywords

EID: 79960842083     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2010.00136     Document Type: Article

References (151)

1. Abplanalp, A. L., Morris, I. R., Parida, B. K., Teale, J. M., and Berton, M. T. (2009). TLR-dependent control of Francisella tularensis infection and host inflammatory responses. PLoS One 4, e7920. doi: 10.1371/journal.pone.0007920.
2. Åhlund, M. K., Ryden, P., Sjöstedt, A., and Stöven, S. (2010). Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster. Infect. Immun. 78, 3118-3128.
3. Al-Khodor, S., and Abu Kwaik, Y. (2010). Triggering Ras signalling by intracellular Francisella tularensis through recruitment of PKCalpha and betaI to the SOS2/GrB2 complex is essential for bacterial proliferation in the cytosol. Cell Microbiol. 12, 1604-1621.
4. Anthony, L. S., Ghadirian, E., Nestel, F. P., and Kongshavn, P. A. (1989). The requirement for gamma interferon in resistance of mice to experimental tularemia. Microb. Pathog. 7, 421-428.
5. Asare, R., and Abu Kwaik, Y. (2010). Molecular complexity orchestrates modulation of phagosome biogenesis and escape to the cytosol of macrophages by Francisella tularensis. Environ. Microbiol. 12, 2559-2586.
6. Aubert, D., Macdonald, D. K., and Valvano, M. A. (2010). BcsKC is an essential protein for the Type VI secretion system activity in Burkholderia cenocepacia that forms an outer membrane complex with BcsLB. J. Biol. Chem. 285, 35988-35998.
7. Ballister, E. R., Lai, A. H., Zuckermann, R. N., Cheng, Y., and Mougous, J. D. (2008). In vitro self-assembly of tailorable nanotubes from a simple protein building block. Proc. Natl. Acad. Sci. U.S.A. 105, 3733-3738.
8. Barbieri, M. A., Kohn, A. D., Roth, R. A., and Stahl, P. D. (1998). Protein kinase B/akt and rab5 mediate Ras activation of endocytosis. J. Biol. Chem. 273, 19367-19370.
9. Barker, J. R., Chong, A., Wehrly, T. D., Yu, J. J., Rodriguez, S. A., Liu, J., Celli, J., Arulanandam, B. P., and Klose, K. E. (2009). The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence. Mol. Microbiol. 74, 1459-1470.
10. Baron, G. S., and Nano, F. E. (1998). MgIA and MgIB are required for the intramacrophage growth of Francisella novicida. Mol. Microbiol. 29, 247-259.
11. Bell, B. L., Mohapatra, N. P., and Gunn, J. S. (2010). Regulation of virulence gene transcripts by the Francisella novicida orphan response regulator PmrA: role of phosphorylation and evidence of MglA/SspA interaction. Infect. Immun. 78, 2189-2198.
12. Bingle, L. E., Bailey, C. M., and Pallen, M. J. (2008). Type VI secretion: a beginner's guide. Curr. Opin. Microbiol. 11, 3-8.
13. Bönemann, G., Pietrosiuk, A., Diemand, A., Zentgraf, H., and Mogk, A. (2009). Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion. EMBO J. 28, 315-325.
14. Bönemann, G., Pietrosiuk, A., and Mogk, A. (2010). Tubules and donuts: a type VI secretion story. Mol. Microbiol. 76, 815-821.
15. Bönquist, L., Lindgren, H., Golovliov, I., Guina, T., and Sjöstedt, A. (2008). MglA and Igl proteins contribute to the modulation of Francisella tularensis live vaccine strain-containing phagosomes in murine macrophages. Infect. Immun. 76, 3502-3510.
16. Bosio, C. M., Bielefeldt-Ohmann, H., and Belisle, J. T. (2007). Active suppression of the pulmonary immune response by Francisella tularensis Schu4. J. Immunol. 178, 4538-4547.
17. Bosio, C. M., and Dow, S. W. (2005). Francisella tularensis induces aberrant activation of pulmonary dendritic cells. J. Immunol. 175, 6792-6801.
18. Boyer, F., Fichant, G., Berthod, J., Vandenbrouck, Y., and Attree, I. (2009). Dissecting the bacterial type VI secretion system by a genome wide in silico analysis: what can be learned from available microbial genomic resources? BMC Genomics 10, 104. doi: 10.1186/1471-2164-10-104.
19. Bröms, J. E., Lavander, M., and Sjöstedt, A. (2009). A conserved Symbol.-1.c65-helix essential for a type VI secretion-like system of Francisella tularensis. J. Bacteriol. 6, 6.
20. Brotcke, A., and Monack, D. M. (2008). Identification of fevR, a novel regulator of virulence gene expression in Francisella novicida. Infect. Immun. 76, 3473-3480.
21. Brotcke, A., Weiss, D. S., Kim, C. C., Chain, P., Malfatti, S., Garcia, E., and Monack, D. M. (2006). Identification of MglA-regulated genes reveals novel virulence factors in Francisella tularensis. Infect. Immun. 74, 6642-6655.
22. Buchan, B. W., McCaffrey, R. L., Lindemann, S. R., Allen, L. A., and Jones, B. D. (2009). Identification of migR, a regulatory element of the Francisella tularensis live vaccine strain iglABCD virulence operon required for normal replication and trafficking in macrophages. Infect. Immun. 77, 2517-2529.
23. Butchar, J. P., Cremer, T. J., Clay, C. D., Gavrilin, M. A., Wewers, M. D., Marsh, C. B., Schlesinger, L. S., and Tridandapani, S. (2008). Microarray analysis of human monocytes infected with Francisella tularensis identifies new targets of host response subversion. PLoS One 3, e2924. doi: 10.1371/ journal.pone.0002924.
24. Castang, S., McManus, H. R., Turner, K. H., and Dove, S. L. (2008). H-NS family members function coordinately in an opportunistic pathogen. Proc. Natl. Acad. Sci. U.S.A. 105, 18947-18952.
25. Champion, M. D., Zeng, Q., Nix, E. B., Nano, F. E., Keim, P., Kodira, C. D., Borowsky, M., Young, S., Koehrsen, M., Engels, R., Pearson, M., Howarth, C., Larson, L., White, J., Alvarado, L., Forsman, M., Bearden, S. W., Sjöstedt, A., Titball, R., Michell, S. L., Birren, B., and Galagan, J. (2009). Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies. PLoS Pathog. 5, e1000459. doi: 10.1371/journal.ppat.1000459.
26. Charity, J. C., Blalock, L. T., Costante-Hamm, M. M., Kasper, D. L., and Dove, S. L. (2009). Small molecule control of virulence gene expression in Francisella tularensis. PLoS Pathog. 5, e1000641. doi: 10.1371/journal. ppat.1000641.
27. Charity, J. C., Costante-Hamm, M. M., Balon, E. L., Boyd, D. H., Rubin, E. J., and Dove, S. L. (2007). Twin RNA polymerase-associated proteins control virulence gene expression in Francisella tularensis. PLoS Pathog. 3, e84. doi: 10.1371/journal. ppat.0030084.
28. Chen, Q., Powell, D. W., Rane, M. J., Singh, S., Butt, W., Klein, J. B., and McLeish, K. R. (2003). Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. J. Immunol. 170, 5302-5308.
29. Chong, A., Wehrly, T. D., Nair, V., Fischer, E. R., Barker, J. R., Klose, K. E., and Celli, J. (2008). The early phagosomal stage of Francisella tularensis determines optimal phagosomal escape and Francisella pathogenicity island protein expression. Infect. Immun. 76, 5488-5499.
30. Chow, J., and Mazmanian, S. K. (2010). A pathobiont of the microbiota balances host colonization and intestinal inflammation. Cell Host Microbe 7, 265-276.
31. Chugani, S., and Greenberg, E. P. (2007). The influence of human respiratory epithelia on Pseudomonas aeruginosa gene expression. Microb. Pathog. 42, 29-35.
32. Clemens, D. L., Lee, B. Y., and Horwitz, M. A. (2004). Virulent and avirulent strains of Francisella tularensis prevent acidification and maturation of their phagosomes and escape into the cytoplasm in human macrophages. Infect. Immun. 72, 3204-3217.
33. Clemens, D. L., Lee, B. Y., and Horwitz, M. A. (2005). Francisella tularensis enters macrophages via a novel process involving pseudopod loops. Infect. Immun. 73, 5892-5902.
34. Clemens, D. L., Lee, B. Y., and Horwitz, M. A. (2009). Francisella tularensis phagosomal escape does not require acidification of the phagosome. Infect. Immun. 77, 1757-1773.
35. Cole, L. E., Elkins, K. L., Michalek, S. M., Qureshi, N., Eaton, L. J., Rallabhandi, P., Cuesta, N., and Vogel, S. N. (2006). Immunologic consequences of Francisella tularensis live vaccine strain infection: role of the innate immune response in infection and immunity. J. Immunol. 176, 6888-6899.
36. Cole, L. E., Santiago, A., Barry, E., Kang, T. J., Shirey, K. A., Roberts, Z. J., Elkins, K. L., Cross, A. S., and Vogel, S. N. (2008). Macrophage proinflammatory response to Francisella tularensis live vaccine strain requires coordination of multiple signaling pathways. J. Immunol. 180, 6885-6891.
37. Cole, L. E., Shirey, K. A., Barry, E., Santiago, A., Rallabhandi, P., Elkins, K. L., Puche, A. C., Michalek, S. M., and Vogel, S. N. (2007). Toll-like receptor 2-mediated signaling requirements for Francisella tularensis live vaccine strain infection of murine macrophages. Infect. Immun. 75, 4127-4137.
38. Crane, D. D., Warner, S. L., and Bosio, C. M. (2009). A novel role for plasminmediated degradation of opsonizing antibody in the evasion of host immunity by virulent, but not attenuated, Francisella tularensis. J. Immunol. 183, 4593-4600.
39. Cremer, T. J., Ravneberg, D. H., Clay, C. D., Piper-Hunter, M. G., Marsh, C. B., Elton, T. S., Gunn, J. S., Amer, A., Kanneganti, T. D., Schlesinger, L. S., Butchar, J. P., and Tridandapani, S. (2009). MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response. PLoS One 4, e8508. doi: 10.1371/journal.pone.0008508.
40. Das, S., Chakrabortty, A., Banerjee, R., Roychoudhury, S., and Chaudhuri, K. (2000). Comparison of global transcription responses allows identification of Vibrio cholerae genes differentially expressed following infection. FEMS Microbiol. Lett. 190, 87-91.
41. Das, S., and 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.
42. de Bruin, O. M., Ludu, J. S., and Nano, F. E. (2007). The Francisella pathogenicity island protein IglA localizes to the bacterial cytoplasm and is needed for intracellular growth. BMC Microbiol. 7, 1. doi: 10.1186/1471-2180-7-1.
43. Dean, R. E., Ireland, P. M., Jordan, J. E., Titball, R. W., and Oyston, P. C. (2009). RelA regulates virulence and intracellular survival of Francisella novicida. Microbiology 155, 4104-4113.
44. Deng, K., Blick, R. J., Liu, W., and Hansen, E. J. (2006). Identification of Francisella tularensis genes affected by iron limitation. Infect. Immun. 74, 4224-4236.
45. Dennis, D. T., Inglesby, T. V., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Fine, A. D., Friedlander, A. M., Hauer, J., Layton, M., Lillibridge, S. R., McDade, J. E., Osterholm, M. T., O'Toole, T., Parker, G., Perl, T. M., Russell, P. K., and Tonat, K. (2001). Tularemia as a biological weapon: medical and public health management. JAMA 285, 2763-2773.
46. Deziel, E., Gopalan, S., Tampakaki, A. P., Lepine, F., Padfield, K. E., Saucier, M., Xiao, G., and Rahme, L. G. (2005). The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl-Lhomoserine lactones. Mol. Microbiol. 55, 998-1014.
47. Dudley, E. G., Thomson, N. R., Parkhill, J., Morin, N. P., and Nataro, J. P. (2006). Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli. Mol. Microbiol. 61, 1267-1282.
48. Edwards, J. A., Rockx-Brouwer, D., Nair, V., and Celli, J. (2009). Restricted cytosolic growth of Francisella tularensis subsp. tularensis by IFN-gamma activation of macrophages. Microbiology 156, 327-339.
49. Fernandes-Alnemri, T., Wu, J., Yu, J. W., Datta, P., Miller, B., Jankowski, W., Rosenberg, S., Zhang, J., and Alnemri, E. S. (2007). The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 14, 1590-1604.
50. Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J., and Alnemri, E. S. (2009). AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509-513.
51. Fernandes-Alnemri, T., Yu, J. W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., Eisenlohr, L., Landel, C. P., and Alnemri, E. S. (2010). The AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat. Immunol. 11, 385-393.
52. Filloux, A. (2009). The type VI secretion system: a tubular story. EMBO J. 28, 309-310.
53. Folkesson, A., Löfdahl, S., and Normark, S. (2002). The Salmonella enterica subspecies I specific centisome 7 genomic island encodes novel protein families present in bacteria living in close contact with eukaryotic cells. Res. Microbiol. 153, 537-545.
54. Fortier, A. H., Slayter, M. V., Ziemba, R., Meltzer, M. S., and Nacy, C. A. (1991). Live vaccine strain of Francisella tularensis: infection and immunity in mice. Infect. Immun. 59, 2922-2928.
55. Gavrilin, M. A., Bouakl, I. J., Knatz, N. L., Duncan, M. D., Hall, M. W., Gunn, J. S., and Wewers, M. D. (2006). Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc. Natl. Acad. Sci. U.S.A. 103, 141-146.
56. Golovliov, I., Baranov, V., Krocova, Z., Kovarova, H., and Sjöstedt, A. (2003a). An attenuated strain of the facultative intracellular bacterium Francisella tularensis can escape the phagosome of monocytic cells. Infect. Immun. 71, 5940-5950.
57. Golovliov, I., Sjöstedt, A., Mokrievich, A., and Pavlov, V. (2003b). A method for allelic replacement in Francisella tularensis. FEMS Microbiol. Lett. 222, 273-280.
58. Golovliov, I., Ericsson, M., Sandström, G., Tärnvik, A., and Sjöstedt, A. (1997). Identification of proteins of Francisella tularensis induced during growth in macrophages and cloning of the gene encoding a prominently induced 23-kilodalton protein. Infect. Immun. 65, 2183-2189.
59. Gray, C. G., Cowley, S. C., Cheung, K. K., and Nano, F. E. (2002). The identification of five genetic loci of Francisella novicida associated with intracellular growth. FEMS Microbiol. Lett. 215, 53-56.
60. Guina, T., Radulovic, D., Bahrami, A. J., Bolton, D. L., Rohmer, L., Jones-Isaac, K. A., Chen, J., Gallagher, L. A., Gallis, B., Ryu, S., Taylor, G. K., Brittnacher, M. J., Manoil, C., and Goodlett, D. R. (2007). MglA regulates Francisella tularensis subsp. novicida (Francisella novicida) response to starvation and oxidative stress. J. Bacteriol. 189, 6580-6586.
61. Henry, T., Brotcke, A., Weiss, D. S., Thompson, L. J., and Monack, D. M. (2007). Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J. Exp. Med. 204, 987-994.
62. Hoyal, C. R., Gutierrez, A., Young, B. M., Catz, S. D., Lin, J. H., Tsichlis, P. N., and Babior, B. M. (2003). Modulation of p47PHOX activity by site-specific phosphorylation: Akt-dependent activation of the NADPH oxidase. Proc. Natl. Acad. Sci. U.S.A. 100, 5130-5135.
63. Hrstka, R., Stulik, J., and Vojtesek, B. (2005). The role of MAPK signal pathways during Francisella tularensis LVS infection-induced apoptosis in murine macrophages. Microbes Infect. 7, 619-625.
64. Ishikawa, T., Rompikuntal, P. K., Lindmark, B., Milton, D. L., and Wai, S. N. (2009). Quorum sensing regulation of the two hcp alleles in Vibrio cholerae O1 strains. PLoS One 4, e6734. doi: 10.1371/ journal.pone.0006734.
65. Jones, J. W., Kayagaki, N., Broz, P., Henry, T., Newton, K., O'Rourke, K., Chan, S., Dong, J., Qu, Y., Roose-Girma, M., Dixit, V. M., and Monack, D. M. (2010). Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc. Natl. Acad. Sci. U.S.A. 107, 9771-9776.
66. Kadzhaev, K., Zingmark, C., Golovliov, I., Bolanowski, M., Shen, H., Conlan, W., and Sjostedt, A. (2009). Identification of genes contributing to the virulence of Francisella tularensis SCHU S4 in a mouse intradermal infection model. PLoS One 4, e5463. doi: 10.1371/journal.pone.0005463.
67. Karlsson, J., Prior, R. G., Williams, K., Lindler, L., Brown, K. A., Chatwell, N., Hjalmarsson, K., Loman, N., Mack, K. A., Pallen, M., Popek, M., Sandström, G., Sjöstedt, A., Svensson, T., Tamas, I., Andersson, S. G., Wren, B. W., Oyston, P. C., and Titball, R. W. (2000). Sequencing of the Francisella tularensis strain Schu 4 genome reveals the shikimate and purine metabolic pathways, targets for the construction of a rationally attenuated auxotrophic vaccine. Microb. Comp. Genomics 5, 25-39.
68. Katz, J., Zhang, P., Martin, M., Vogel, S. N., and Michalek, S. M. (2006). Toll-like receptor 2 is required for inflammatory responses to Francisella tularensis LVS. Infect. Immun. 74, 2809-2816.
69. Kawula, T. H., Hall, J. D., Fuller, J. R., and Craven, R. R. (2004). Use of transposon-transposase complexes to create stable insertion mutant strains of Francisella tularensis LVS. Appl. Environ. Microbiol. 70, 6901-6904.
70. Keim, P., Johansson, A., and Wagner, D. M. (2007). Molecular epidemiology, evolution, and ecology of Francisella. Ann. N.Y. Acad. Sci. 1105, 30-66.
71. Kostyuchenko, V. A., Chipman, P. R., Leiman, P. G., Arisaka, F., Mesyanzhinov, V. V., and Rossmann, M. G. (2005). The tail structure of bacteriophage T4 and its mechanism of contraction. Nat. Struct. Mol. Biol. 12, 810-813.
72. Kraemer, P. S., Mitchell, A., Pelletier, M. R., Gallagher, L. A., Wasnick, M., Rohmer, L., Brittnacher, M. J., Manoil, C., Skerett, S. J., and Salama, N. R. (2009). Genome-wide screen in Francisella novicida for genes required for pulmonary and systemic infection in mice. Infect. Immun. 77, 232-244.
73. Lai, X. H., Golovliov, I., and Sjöstedt, A. (2004). Expression of IglC is necessary for intracellular growth and induction of apoptosis in murine macrophages by Francisella tularensis. Microb. Pathog. 37, 225-230.
74. Lai, X. H., and Sjöstedt, A. (2003). Delineation of the molecular mechanisms of Francisella tularensis-induced apoptosis in murine macrophages. Infect. Immun. 71, 4642-4646.
75. Larsson, P., Elfsmark, D., Svensson, K., Wikström, P., Forsman, M., Brettin, T., Keim, P., and Johansson, A. (2009). Molecular evolutionary consequences of niche restriction in Francisella tularensis, a facultative intracellular pathogen. PLoS Pathog. 5, e1000472. doi: 10.1371/journal.ppat.1000472.
76. Lauriano, C. M., Barker, J. R., Nano, F. E., Arulanandam, B. P., and Klose, K. E. (2003). Allelic exchange in Francisella tularensis using PCR products. FEMS Microbiol. Lett. 229, 195-202.
77. Lauriano, C. M., Barker, J. R., Yoon, S. S., Nano, F. E., Arulanandam, B. P., Hassett, D. J., and Klose, K. E. (2004). MglA regulates transcription of virulence factors necessary for Francisella tularensis intraamoebae and intramacrophage survival. Proc. Natl. Acad. Sci. U.S.A. 101, 4246-4249.
78. Leiman, P. G., Basler, M., Ramagopal, U. A., Bonanno, J. B., Sauder, J. M., Pukatzki, S., Burley, S. K., Almo, S. C., and Mekalanos, J. J. (2009). Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin. Proc. Natl. Acad. Sci. U.S.A. 106, 4154-4159.
79. Lenco, J., Hubalek, M., Larsson, P., Fucikova, A., Brychta, M., Macela, A., and Stulik, J. (2007). Proteomics analysis of the Francisella tularensis LVS response to iron restriction: induction of the F. tularensis pathogenicity island proteins IglABC. FEMS Microbiol. Lett. 269, 11-21.
80. Lenco, J., Pavkova, I., Hubalek, M., and Stulik, J. (2005). Insights into the oxidative stress response in Francisella tularensis LVS and its mutant DeltaiglC1 + 2 by proteomics analysis. FEMS Microbiol. Lett. 246, 47-54.
81. Lesic, B., Starkey, M., He, J., Hazan, R., and Rahme, L. G. (2009). Quorum sensing differentially regulates Pseudomonas aeruginosa type VI secretion locus I and homologous loci II and III, which are required for pathogenesis. Microbiology 155, 2845-2855.
82. Li, H., Nookala, S., Bina, X. R., Bina, J. E., and Re, F. (2006). Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation. J. Leukoc. Biol. 80, 766-773.
83. Lindgren, H., Golovliov, I., Baranov, V., Ernst, R. K., Telepnev, M., and Sjöstedt, A. (2004). Factors affecting the escape of Francisella tularensis from the phagolysosome. J. Med. Microbiol. 53, 953-958.
84. Lucchini, S., Rowley, G., Goldberg, M. D., Hurd, D., Harrison, M., and Hinton, J. C. (2006). H-NS mediates the silencing of laterally acquired genes in bacteria. PLoS Pathog. 2, e81. doi: 10.1371/ journal.ppat.0020081.
85. Ludu, J. S., de Bruin, O. M., Duplantis, B. N., Schmerk, C. L., Chou, A. Y., Elkins, K. L., and Nano, F. E. (2008). The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system. J. Bacteriol. 190, 4584-4595.
86. Ma, L. S., Lin, J. S., and 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 system-mediated Hcp secretion in Agrobacterium tumefaciens. J. Bacteriol. 191, 4316-4329.
87. Maier, T. M., Casey, M. S., Becker, R. H., Dorsey, C. W., Glass, E. M., Maltsev, N., Zahrt, T. C., and Frank, D. W. (2007). Identification of Francisella tularensis Himar1-based transposon mutants defective for replication in macrophages. Infect. Immun. 75, 5376-5389.
88. Mariathasan, S., Newton, K., Monack, D. M., Vucic, D., French, D. M., Lee, W. P., Roose-Girma, M., Erickson, S., and Dixit, V. M. (2004). Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 430, 213-218.
89. Mariathasan, S., Weiss, D. S., Newton, K., McBride, J., O'Rourke, K., Roose-Girma, M., Lee, W. P., Weinrauch, Y., Monack, D. M., and Dixit, V. M. (2006). Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228-232.
90. McCaffrey, R. L., and Allen, L. A. (2006). Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. J. Leukoc. Biol. 80, 1224-1230.
91. Meibom, K. L., and Charbit, A. (2009). The unraveling panoply of Francisella tularensis virulence attributes. Curr. Opin. Microbiol. 13, 11-17.
92. Meibom, K. L., Forslund, A. L., Kuoppa, K., Alkhuder, K., Dubail, I., Dupuis, M., Forsberg, Å., and Charbit, A. (2009). Hfq, a novel pleiotropic regulator of virulence-associated genes in Francisella tularensis. Infect. Immun. 77, 1866-1880.
93. Melillo, A., Sledjeski, D. D., Lipski, S., Wooten, R. M., Basrur, V., and Lafontaine, E. R. (2006). Identification of a Francisella tularensis LVS outer membrane protein that confers adherence to A549 human lung cells. FEMS Microbiol. Lett. 263, 102-108.
94. Mohapatra, N. P., Soni, S., Bell, B. L., Warren, R., Ernst, R. K., Muszynski, A., Carlson, R. W., and Gunn, J. S. (2007). Identification of an orphan response regulator required for the virulence of Francisella spp. and transcription of pathogenicity island genes. Infect. Immun. 75, 3305-3314.
95. Mohapatra, N. P., Soni, S., Rajaram, M. V., Dang, P. M., Reilly, T. J., El-Benna, J., Clay, C. D., Schlesinger, L. S., and Gunn, J. S. (2010). Francisella acid phosphatases inactivate the NADPH oxidase in human phagocytes. J. Immunol. 184, 5141-5150.
96. Mörner, T., and Addison, E. (2001). "Tularemia," in Infectious Diseases of Wild Animals, 3rd Edn., ed. B. I. Williams (Ames, Iowa: Iowa State University), 303-312.
97. Mougous, J. D., Cuff, M. E., Raunser, S., Shen, A., Zhou, M., Gifford, C. A., Goodman, A. L., Joachimiak, G., Ordonez, C. L., Lory, S., Walz, T., Joachimiak, A., and Mekalanos, J. J. (2006). A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526-1530.
98. Nano, F. E., and Schmerk, C. (2007). The Francisella pathogenicity island. Ann. N.Y. Acad. Sci. 1105, 122-137.
99. Nano, F. E., Zhang, N., Cowley, S. C., Klose, K. E., Cheung, K. K., Roberts, M. J., Ludu, J. S., Letendre, G. W., Meierovics, A. I., Stephens, G., and Elkins, K. L. (2004). A Francisella tularensis pathogenicity island required for intramacrophage growth. J. Bacteriol. 186, 6430-6436.
100. Oyston, P. C., Sjöstedt, A., and Titball, R. W. (2004). Tularaemia: bioterrorism defence renews interest in Francisella tularensis. Nat. Rev. Microbiol. 2, 967-978.
101. Parsa, K. V., Butchar, J. P., Rajaram, M. V., Cremer, T. J., Gunn, J. S., Schlesinger, L. S., and Tridandapani, S. (2008). Francisella gains a survival advantage within mononuclear phagocytes by suppressing the host IFN-gamma response. Mol. Immunol. 45, 3428-3437.
102. Parsa, K. V., Ganesan, L. P., Rajaram, M. V., Gavrilin, M. A., Balagopal, A., Mohapatra, N. P., Wewers, M. D., Schlesinger, L. S., Gunn, J. S., and Tridandapani, S. (2006). Macrophage pro-inflammatory response to Francisella novicida infection is regulated by SHIP. PLoS Pathog. 2, e71. doi: 10.1371/journal.ppat.0020071.
103. Parsons, D. A., and Heffron, F. (2005). sciS, an icmF homolog in Salmonella enterica serovar Typhimurium, limits intracellular replication and decreases virulence. Infect. Immun. 73, 4338-4345.
104. Pell, L. G., Kanelis, V., Donaldson, L. W., Howell, P. L., and Davidson, A. R. (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. U.S.A. 106, 4160-4165.
105. Prior, R. G., Klasson, L., Larsson, P., Williams, K., Lindler, L., Sjöstedt, A., Svensson, T., Tamas, I., Wren, B. W., Oyston, P. C., Andersson, S. G., and Titball, R. W. (2001). Preliminary analysis and annotation of the partial genome sequence of Francisella tularensis strain Schu 4. J. Appl. Microbiol. 91, 614-620.
106. Pukatzki, S., Ma, A. T., Revel, A. T., Sturtevant, D., and Mekalanos, J. J. (2007). Type VI secretion system translocates a phage tail spike-like protein into target cells where it crosslinks actin. Proc. Natl. Acad. Sci. U.S.A. 104, 15508-15513.
107. Pukatzki, S., Ma, A. T., Sturtevant, D., Krastins, B., Sarracino, D., Nelson, W. C., Heidelberg, J. F., and Mekalanos, J. J. (2006). Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc. Natl. Acad. Sci. U.S.A. 103, 1528-1533.
108. Pukatzki, S., McAuley, S. B., and Miyata, S. T. (2009). The type VI secretion system: translocation of effectors and effector-domains. Curr. Opin. Microbiol. 12, 11-17.
109. Qin, A., and Mann, B. J. (2006). Identification of transposon insertion mutants of Francisella tularensis tularensis strain Schu S4 deficient in intracellular replication in the hepatic cell line HepG2. BMC Microbiol. 6, 69. doi: 10.1186/1471-2180-6-69.
110. Qin, A., Scott, D. W., Thompson, J. A., and Mann, B. J. (2009). Identification of an essential Francisella tularensis subsp. tularensis virulence factor. Infect. Immun. 77, 152-161.
111. Rajaram, M. V., Butchar, J. P., Parsa, K. V., Cremer, T. J., Amer, A., Schlesinger, L. S., and Tridandapani, S. (2009). Akt and SHIP modulate Francisella escape from the phagosome and induction of the Fas-mediated death pathway. PLoS One 4, e7919. doi: 10.1371/journal. pone.0007919
112. Rajaram, M. V., Ganesan, L. P., Parsa, K. V., Butchar, J. P., Gunn, J. S., and Tridandapani, S. (2006). Akt/Protein kinase B modulates macrophage inflammatory response to Francisella infection and confers a survival advantage in mice. J. Immunol. 177, 6317-6324.
113. Rathinam, V. A., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., Hornung, V., Vogel, S. N., Szomolanyi-Tsuda, E., and Fitzgerald, K. A. (2010). The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395-402.
114. Ray, K., Marteyn, B., Sansonetti, P. J., and Tang, C. M. (2009). Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nat. Rev. Microbiol. 7, 333-340.
115. Read, A., Vogl, S. J., Hueffer, K., Gallagher, L. A., and Happ, G. M. (2008). Francisella genes required for replication in mosquito cells. J. Med. Entomol. 45, 1108-1116.
116. Rodriguez, S. A. (2010). Genetic Regulation of Virulence in Francisella tularensis. Doctoral thesis, the University of Texas, San Antonio.
117. Roth, K. M., Gunn, J. S., Lafuse, W., and Satoskar, A. R. (2009). Francisella inhibits STAT1-mediated signaling in macrophages and prevents activation of antigen-specific T cells. Int. Immunol. 21, 19-28.
118. Sammons-Jackson, W. L., McClelland, K., Manch-Citron, J. N., Metzger, D. W., Bakshi, C. S., Garcia, E., Rasley, A., and Anderson, B. E. (2008). Generation and characterization of an attenuated mutant in a response regulator gene of Francisella tularensis live vaccine strain (LVS). DNA Cell Biol. 27, 387-403.
119. Santic, M., Akimana, C., Asare, R., Kouokam, J. C., Atay, S., and Kwaik, Y. A. (2009). Intracellular fate of Francisella tularensis within arthropod-derived cells. Environ. Microbiol. 11, 1473-1481.
120. Santic, M., Asare, R., Skrobonja, I., Jones, S., and Abu Kwaik, Y. (2008). Acquisition of the vATPase proton pump and phagosome acidification is essential for escape of Francisella tularensis into the macrophage cytosol. Infect. Immun. 7, 7.
121. Santic, M., Molmeret, M., and Abu Kwaik, Y. (2005a). Modulation of biogenesis of the Francisella tularensis subsp. novicida-containing phagosome in quiescent human macrophages and its maturation into a phagolysosome upon activation by IFN-gamma. Cell Microbiol. 7, 957-967.
122. Santic, M., Molmeret, M., Klose, K. E., Jones, S., and Kwaik, Y. A. (2005b). The Francisella tularensis pathogenicity island protein IglC and its regulator MglA are essential for modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm. Cell Microbiol. 7, 969-979.
123. Santic, M., Molmeret, M., Barker, J. R., Klose, K. E., Dekanic, A., Doric, M., and Abu Kwaik, Y. (2007). A Francisella tularensis pathogenicity island protein essential for bacterial proliferation within the host cell cytosol. Cell Microbiol. 9, 2391-2403.
124. Schell, M. A., Ulrich, R. L., Ribot, W. J., Brueggemann, E. E., Hines, H. B., Chen, D., Lipscomb, L., Kim, H. S., Mrazek, J., Nierman, W. C., and Deshazer, D. (2007). Type VI secretion is a major virulence determinant in Burkholderia mallei. Mol. Microbiol. 64, 1466-1485.
125. Schlieker, C., Zentgraf, H., Dersch, P., and Mogk, A. (2005). ClpV, a unique Hsp100/Clp member of pathogenic proteobacteria. Biol. Chem. 386, 1115-1127.
126. Schmerk, C. L., Duplantis, B. N., Howard, P. L., and Nano, F. E. (2009a). A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1. Microbiology 155, 1498-1504.
127. Schmerk, C. L., Duplantis, B. N., Wang, D., Burke, R. D., Chou, A. Y., Elkins, K. L., Ludu, J. S., and Nano, F. E. (2009b). Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida. Microbiology 155, 1489-1497.
128. Sexton, J. A., Miller, J. L., Yoneda, A., Kehl-Fie, T. E., and Vogel, J. P. (2004). Legionella pneumophila DotU and IcmF are required for stability of the Dot/Icm complex. Infect. Immun. 72, 5983-5992.
129. Shalom, G., Shaw, J. G., and Thomas, M. S. (2007). In vivo expression technology identifies a type VI secretion system locus in Burkholderia pseudomallei that is induced upon invasion of macrophages. Microbiology 153, 2689-2699.
130. Shrivastava, S., and Mande, S. S. (2008). Identification and functional characterization of gene components of Type VI Secretion system in bacterial genomes. PLoS One 3, e2955. doi: 10.1371/journal.pone.0002955
131. Su, J., Yang, J., Zhao, D., Kawula, T. H., Banas, J. A., and Zhang, J. R. (2007). Genome-wide identification of Francisella tularensis virulence determinants. Infect. Immun. 75, 3089-3101.
132. Suarez, G., Sierra, J. C., Sha, J., Wang, S., Erova, T. E., Fadl, A. A., Foltz, S. M., Horneman, A. J., and Chopra, A. K. (2008). Molecular characterization of a functional type VI secretion system from a clinical isolate of Aeromonas hydrophila. Microb. Pathog. 44, 344-361.
133. Sun, G. W., Chen, Y., Liu, Y., Tan, G. Y., Ong, C., Tan, P., and Gan, Y. H. (2010). Identification of a regulatory cascade controlling Type III Secretion System 3 gene expression in Burkholderia pseudomallei. Mol. Microbiol. 76, 677-689.
134. Sun, P., Austin, B. P., Schubot, F. D., and Waugh, D. S. (2007). New protein fold revealed by a 1.65 A resolution crystal structure of Francisella tularensis pathogenicity island protein IglC. Protein Sci. 16, 2560-2563.
135. Syed, K. A., Beyhan, S., Correa, N., Queen, J., Liu, J., Peng, F., Satchell, K. J., Yildiz, F., and Klose, K. E. (2009). The Vibrio cholerae flagellar regulatory hierarchy controls expression of virulence factors. J. Bacteriol. 191, 6555-6570.
136. Tärnvik, A. (1989). Nature of protective immunity to Francisella tularensis. Rev. Infect. Dis. 11, 440-451.
137. Tatusov, R. L., Galperin, M. Y., Natale, D. A., and Koonin, E. V. (2000). The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res. 28, 33-36.
138. Telepnev, M., Golovliov, I., Grundström, T., Tärnvik, A., and Sjöstedt, A. (2003). Francisella tularensis inhibits Tolllike receptor-mediated activation of intracellular signalling and secretion of TNF-alpha and IL-1 from murine macrophages. Cell Microbiol. 5, 41-51.
139. Telepnev, M., Golovliov, I., and Sjöstedt, A. (2005). Francisella tularensis LVS initially activates but subsequently down-regulates intracellular signaling and cytokine secretion in mouse monocytic and human peripheral blood mononuclear cells. Microb. Pathog. 38, 239-247.
140. Tempel, R., Lai, X. H., Crosa, L., Kozlowicz, B., and Heffron, F. (2006). Attenuated Francisella novicida transposon mutants protect mice against wildtype challenge. Infect. Immun. 74, 5095-5105.
141. Thakran, S., Li, H., Lavine, C. L., Miller, M. A., Bina, J. E., Bina, X. R., and Re, F. (2008). Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2/TLR1 heterodimer. J. Biol. Chem. 283, 3751-3760.
142. Twine, S., Byström, M., Chen, W., Forsman, M., Golovliov, I., Johansson, A., Kelly, J., Lindgren, H., Svensson, K., Zingmark, C., Conlan, W., and Sjöstedt, A. (2005). A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine. Infect. Immun. 73, 8345-8352.
143. Twine, S. M., Mykytczuk, N. C., Petit, M. D., Shen, H., Sjöstedt, A., Wayne Conlan, J., and Kelly, J. F. (2006). In vivo proteomic analysis of the intracellular bacterial pathogen, Francisella tularensis, isolated from mouse spleen. Biochem. Biophys. Res. Commun. 345, 1621-1633.
144. Ulland, T. K., Buchan, B. W., Ketterer, M. R., Fernandes-Alnemri, T., Meyerholz, D. K., Apicella, M. A., Alnemri, E. S., Jones, B. D., Nauseef, W. M., and Sutterwala, F. S. (2010). Cutting edge: mutation of Francisella tularensis mviN leads to increased macrophage absent in melanoma 2 inflammasome activation and a loss of virulence. J. Immunol. 185, 2670-2674.
145. Vonkavaara, M., Telepnev, M. V., Ryden, P., Sjöstedt, A., and Stöven, S. (2008). Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis. Cell Microbiol. 10, 1327-1338.
146. Wehrly, T. D., Chong, A., Virtaneva, K., Sturdevant, D. E., Child, R., Edwards, J. A., Brouwer, D., Nair, V., Fischer, E. R., Wicke, L., Curda, A. J., Kupko, J. J., 3rd, Martens, C., Crane, D. D., Bosio, C. M., Porcella, S. F., and Celli, J. (2009). Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages. Cell Microbiol. 11, 1128-1150.
147. Weiss, D. S., Brotcke, A., Henry, T., Margolis, J. J., Chan, K., and Monack, D. M. (2007). In vivo negative selection screen identifies genes required for Francisella virulence. Proc. Natl. Acad. Sci. U.S.A. 104, 6037-6042.
148. Wickstrum, J. R., Bokhari, S. M., Fischer, J. L., Pinson, D. M., Yeh, H. W., Horvat, R. T., and Parmely, M. J. (2009). Francisella tularensis induces extensive caspase-3 activation and apoptotic cell death in the tissues of infected mice. Infect. Immun. 77, 4827-4836.
149. Woolard, M. D., Hensley, L. L., Kawula, T. H., and Frelinger, J. A. (2008). Respiratory Francisella tularensis live vaccine strain infection induces Th17 cells and prostaglandin E2, which inhibits generation of gamma interferon-positive T cells. Infect. Immun. 76, 2651-2659.
150. Wu, H. Y., Chung, P. C., Shih, H. W., Wen, S. R., and Lai, E. M. (2008). Secretome analysis uncovers an Hcp-family protein secreted via a type VI secretion system in Agrobacterium tumefaciens. J. Bacteriol. 190, 2841-2850.
151. Zheng, J., and Leung, K. Y. (2007). Dissection of a type VI secretion system in Edwardsiella tarda. Mol. Microbiol. 66, 1192-1206.