Legionella pneumophila - A human pathogen that co-evolved with fresh water protozoa

Cellular and Molecular Life Sciences

Volumn 64, Issue 4, 2007, Pages 432-448

  Albert Weissenberger, C ^a,b   Cazalet, C ^a   Buchrieser, C ^a  

^a INSTITUT PASTEUR   (France)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

Eukaryotic like proteins; Legionella pneumophila; Legionnaires disease; Pathogenesis

Indexed keywords

FRESH WATER; MEMBRANE PROTEIN;

AMINO ACID SEQUENCE; BACTERIAL FLAGELLUM; BACTERIAL VIRULENCE; CELL MEMBRANE; COEVOLUTION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC REGULATION; GENOME; GENOME ANALYSIS; GENOMICS; LEGIONELLA PNEUMOPHILA; LIFE CYCLE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PROTOZOON; REVIEW;

ANIMALS; BACTERIAL PROTEINS; EVOLUTION; FRESH WATER; HUMANS; LEGIONELLA PNEUMOPHILA; PROTOZOA; VIRULENCE FACTORS;

BACTERIA (MICROORGANISMS); EUKARYOTA; LEGIONELLA; LEGIONELLA PNEUMOPHILA; PROTOZOA;

EID: 33847266240     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-006-6391-1     Document Type: Review

References (137)

1. Fields B. S., Benson R. F. and Besser R. E. (2002) Legionella and Legionnaires' disease: 25 years of investigation. Clin. Microbiol. Rev. 15: 506 - 526
2. Benson R. F. and Fields B. S. (1998) Classification of the genus Legionella. Semin. Respir. Infect. 13, 90 - 99
3. Fliermans C. B., Cherry W. B., Orrison L. H., Smith S. J., Tison D. L. and Pope D. H. (1981) Ecological distribution of Legionella pneumophila. Appl. Environ. Microbiol. 41, 9 - 16
4. Rowbotham T. J. (1980) Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae. J. Clin. Pathol. 33, 1179 - 1183
5. Abu Kwaik Y., Gao L. Y., Stone B. J., Venkataraman C. and Harb O. S. (1998) Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis. Appl. Environ. Microbiol. 64, 3127 - 3133
6. Fields B. S. (1993) Legionella and protozoa: Interaction of a pathogen and its natural host. ASM Press, Washington D.C.
7. Fields B. S. (1996) The molecular ecology of Legionellae. Trends Microbiol. 4, 286 - 290
8. Fraser D. W., Tsai T. R., Orenstein W., Parkin W. E., Beecham H. J., Sharrar R. G., Harris J., Mallison G. F., Martin S. M., McDade J. E., Shepard C. C. and Brachman P. S. (1977) Legionnaires' disease: description of an epidemic of pneumonia. N. Engl. J. Med. 297, 1189 - 1197
9. Doleans A., Aurell H., Reyrolle M., Lina G., Freney J., Vandenesch F., Etienne J. and Jarraud S. (2004) Clinical and environmental distributions of Legionella strains in France are different. J. Clin. Microbiol. 42, 458 - 460
10. Yu V. L., Plouffe J. F., Pastoris M. C., Stout J. E., Schousboe M., Widmer A., Summersgill J., File T., Heath C. M., Paterson D. L. and Chereshsky A. (2002) Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey. J. Infect. Dis. 186, 127 - 128
11. Muder R. R. and Yu V. L. (2002) Infection due to Legionella species other than L. pneumophila. Clin. Infect. Dis. 35, 990 - 998
12. Atlas R. M. (1999) Legionella: from environmental habitats to disease pathology, detection and control. Environ. Microbiol. 1, 283 - 293
13. Horwitz M. A. (1983) The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J. Exp. Med. 158, 2108-2126
14. Horwitz M. A. and Maxfield F. R. (1984) Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J. Cell. Biol. 99, 1936 - 1943
15. Sturgill-Koszycki S. and Swanson M. S. (2000) Legionella pneumophila replication vacuoles mature into acidic, endocytic organelles. J. Exp. Med. 192, 1261 - 1272
16. Sauer J. D., Shannon J. G., Howe D., Hayes S. F., Swanson M. S. and Heinzen R. A. (2005) Specificity of Legionella pneumophila and Coxiella burnetii vacuoles and versatility of Legionella pneumophila revealed by coinfection. Infect. Immun. 73, 4494 - 4504
17. Byrne B. and Swanson M. S. (1998) Expression of Legionella pneumophila virulence traits in response to growth conditions. Infect. Immun. 66, 3029 - 3034
18. Molofsky A. B. and Swanson M. S. (2004) Differentiate to thrive: lessons from the Legionella pneumophila life cycle. Mol. Microbiol. 53, 29 - 40
19. Swanson M. S. and Hammer B. K. (2000) Legionella pneumophila pathogenesis: a fateful journey from amoebae to macrophages. Annu. Rev. Microbiol. 54, 567 - 613
20. Swanson M. S. and Fernandez-Moreira E. (2002) A microbial strategy to multiply in macrophages: the pregnant pause. Traffic 3, 170 - 177
21. Cazalet C., Rusniok C., Bruggemann H., Zidane N., Magnier A., Ma L., Tichit M., Jarraud S., Bouchier C., Vandenesch F., Kunst F., Etienne J., Glaser P. and Buchrieser C. (2004) Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 36, 1165 - 1173
22. Chien M., Morozova I., Shi S., Sheng H., Chen J., Gomez S. M., Asamani G., Hill K., Nuara J., Feder M., Rineer J., Greenberg J. J., Steshenko V., Park S. H., Zhao B., Teplitskaya E., Edwards J. R., Pampou S., Georghiou A., Chou I. C., Iannuccilli W., Ulz M. E., Kim D. H., Geringer-Sameth A., Goldsberry C., Morozov P., Fischer S. G., Segal G., Qu X., Rzhetsky A., Zhang P., Cayanis E., De Jong P. J., Ju J., Kalachikov S., Shuman H. A. and Russo J. J. (2004) The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305, 1966 - 1968
23. Brüggemann H., Hagman A., Jules M., Sismeiro O., Dillies M., Gouyette C., Kunst F., Steinert M., Heuner K., Coppee J. Y. and Buchrieser C. (2006) Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila. Cell. Microbiol. 8, 1228 - 1240
24. Garduno R. A., Garduno E., Hiltz M. and Hoffman P. S. (2002) Intracellular growth of Legionella pneumophila gives rise to a differentiated form dissimilar to stationary-phase forms. Infect. Immun. 70, 6273 - 6283
25. Piao Z., Sze C. C., Barysheva O., Iida K. and Yoshida S. (2006) Temperature-regulated formation of mycelial mat-like biofilms by Legionella pneumophila. Appl. Environ. Microbiol. 72, 1613 - 1622
26. Murga R., Forster T. S., Brown E., Pruckler J. M., Fields B. S. and Donlan R. M. (2001) Role of biofilms in the survival of Legionella pneumophila in a model potable-water system. Microbiology 147, 3121 - 3126
27. Kuiper M. W., Wullings B. A., Akkermans A. D., Beumer R. R. and van der Kooij D. (2004) Intracellular proliferation of Legionella pneumophila in Hartmannella vermiformis in aquatic biofilms grown on plasticized polyvinyl chloride. Appl. Environ. Microbiol. 70, 6826 - 6833
28. Romeo T. (1998) Global regulation by the small RNA-binding protein CsrA and the non-coding RNA molecule CsrB. Mol. Microbiol. 29, 1321 - 1330
29. Fettes P. S., Forsbach-Birk, V., Lynch D. and Marre R. (2001) Overexpression of a Legionella pneumophila homologue of the E. coli regulator csrA affects cell size, flagellation, and pigmentation. Int. J. Med. Microbiol. 291, 353 - 360
30. Molofsky A. B. and Swanson M. S. (2003) Legionella pneumophila CsrA is a pivotal repressor of transmission traits and activator of replication. Mol. Microbiol. 50, 445 - 461
31. Majdalani N., Vanderpool C. K. and Gottesman S. (2005) Bacterial small RNA regulators. Crit. Rev. Biochem. Mol. Biol. 40, 93 - 113
32. Heeb S. and Haas D. (2001) Regulatory roles of the GacS/GacA two-component system in plant-associated and other gram-negative bacteria. Mol. Plant. Microbe Interact. 14, 1351 - 1363
33. Hammer B. K., Tateda E. S. and Swanson M. S. (2002) A two-component regulator induces the transmission phenotype of stationary-phase Legionella pneumophila. Mol. Microbiol. 44, 107 - 118
34. Lynch D., Fieser N., Gloggler K., Forsbach-Birk V. and Marre R. (2003) The response regulator LetA regulates the stationary-phase stress response in Legionella pneumophila and is required for efficient infection of Acanthamoeba castellanii. FEMS Microbiol. Lett. 219, 241 - 248
35. Kulkarni P. R., Cui X., Williams J. W., Stevens A. M. and Kulkarni R. V. (2006) Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri. Nucleic Acids Res. 34, 3361 - 3369
36. Bachman M. A. and Swanson M. S. (2004) The LetE protein enhances expression of multiple LetA/LetS-dependent transmission traits by Legionella pneumophila. Infect. Immun. 72, 3284 - 3293
37. Hammer B. K. and Swanson M. S. (1999) Co-ordination of Legionella pneumophila virulence with entry into stationary phase by ppGpp. Mol. Microbiol. 33, 721 - 731
38. Jain V., Kumar M. and Chatterji D. (2006) ppGpp: stringent response and survival. J. Microbiol. 44, 1 - 10
39. Zusman T., Gal-Mor O. and Segal G. (2002) Characterization of a Legionella pneumophila relA insertion mutant and toles of RelA and RpoS in virulence gene expression. J. Bacteriol. 184, 67 - 75
40. McNealy T. L., Forsbach-Birk V., Shi C. and Marre R. (2005) The Hfq homolog in Legionella pneumophila demonstrates regulation by LetA and RpoS and interacts with the global regulator CsrA. J. Bacteriol. 187, 1527 - 1532
41. Abu-Zant A., Asare R., Graham J. E. and Abu Kwaik Y. (2006) Role for RpoS but not RelA of Legionella pneumophila in modulation of phagosome biogenesis and adaptation to the phagosomal microenvironment. Infect. Immun. 74, 3021 - 3026
42. Bachman M. A. and Swanson M. S. (2001) RpoS co-operates with other factors to induce Legionella pneumophila virulence in the stationary phase. Mol. Microbiol. 40, 1201 - 1214
43. Bachman M. A. and Swanson M. S. (2004) Genetic evidence that Legionella pneumophila RpoS modulates expression of the transmission phenotype in both the exponential phase and the stationary phase. Infect. Immun. 72, 2468 - 2476
44. Gal-Mor O. and Segal G. (2003) The Legionella pneumophila GacA homolog (LetA) is involved in the regulation of icm virulence genes and is required for intracellular multiplication in Acanthamoeba castellanii. Microb. Pathog. 34, 187 - 194
45. Hales L. M. and Shuman H. A. (1999) The Legionella pneumophila rpoS gene is required for growth within Acanthamoeba castellanii. J. Bacteriol. 181, 4879 - 4889
46. Broich M., Rydzewski K., McNealy T. L., Marre R. and Flieger A. (2006) The global regulatory proteins LetA and RpoS control phospholipase A, lysophospholipase A, acyltransferase, and other hydrolytic activities of Legionella pneumophila JR32. J. Bacteriol. 188, 1218 - 1226
47. Soutourina O. A. and Bertin P. N. (2003) Regulation cascade of flagellar expression in Gram-negative bacteria. FEMS Microbiol. Rev. 27, 505 - 523
48. Dasgupta N. and Ramphal R. (2001) Interaction of the antiactivator FleN with the transcriptional activator FleQ regulates flagellar number in Pseudomonas aeruginosa. J. Bacteriol. 183, 6636 - 6644
49. Jacobi S., Schade R. and Heuner K. (2004) Characterization of the alternative sigma factor sigma54 and the transcriptional regulator FleQ of Legionella pneumophila, which are both involved in the regulation cascade of flagellar gene expression. J. Bacteriol. 186, 2540-2547
50. Heuner K. and Steinert M. (2003) The flagellum of Legionella pneumophila and its link to the expression of the virulent phenotype. Int. J. Med. Microbiol. 293, 133 - 143
51. Aldridge P., Karlinsey J. and Hughes K. T. (2003) The type III secretion chaperone FlgN regulates flagellar assembly via a negative feedback loop containing its chaperone substrates FlgK and FlgL. Mol. Microbiol. 49, 1333 - 1345
52. Molofsky A. B., Shetron-Rama L. M. and Swanson M. S. (2005) Components of the Legionella pneumophila flagellar regulon contribute to multiple virulence traits, including lysosome avoidance and macrophage death. Infect. Immun. 73, 5720 - 5734
53. Molofsky A. B., Byrne B. G., Whitfield N. N., Madigan C. A., Fuse E. T., Tateda K. and Swanson M. S. (2006) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. J. Exp. Med. 17, 1093 - 1104
54. Ren T., Zamboni D. S., Roy C. R., Dietrich W. F. and Vance R. E. (2006) Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog. 2, e18
55. Heuner K., Dietrich C., Skriwan C., Steinert M. and Hacker J. (2002) Influence of the alternative sigma(28) factor on virulence and flagellum expression of Legionella pneumophila. Infect. Immun. 70, 1604-1608
56. Brüggemann H., Cazalet C. and Buchrieser C. (2006) Adaptation of Legionella pneumophila to the host environment: role of protein secretion, effectors and eukaryotic-like proteins. Curr. Opin. Microbiol. 9, 86 - 94
57. de Felipe K. S., Pampou S., Jovanovic O. S., Pericone C. D., Ye S. F., Kalachikov S. and Shuman HA. (2005) Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187, 7716 - 7726
58. Cazalet C., Jarraud S., Ghavi-Helm Y., Allignet J., Kunst F., Etienne J., Glaser P. and Buchrieser C. (2006) Genetic diversity of the species Legionella pneumophila. ASM Press, Washington D.C.
59. Seshadri R., Paulsen I. T., Eisen J. A., Read T. D., Nelson K. E., Nelson W. C., Ward N. L., Tettelin H., Davidsen T. M., Beanan M. J., Deboy R. T., Daugherty S. C., Brinkac L. M., Madupu R., Dodson R. J., Khouri H. M., Lee K. H., Carty H. A., Scanlan D., Heinzen R. A., Thompson H. A., Samuel J. E., Fraser C. M. and Heidelberg J. F. (2003) Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc. Natl. Acad. Sci. USA 100, 5455 - 5460
60. Wu M., Sun L. V., Vamathevan J., Riegler M., Deboy R., Brownlie J. C., McGraw E. A., Martin W., Esser C., Ahmadinejad N., Wiegand C., Madupu R., Beanan M. J., Brinkac L. M., Daugherty S. C., Durkin A. S., Kolonay J. F., Nelson W. C., Mohamoud Y., Lee P., Berry K., Young M. B., Utterback T., Weidman J., Nierman W. C., Paulsen I. T., Nelson K. E., Tettelin H., O'Neill S. L. and Eisen J. A. (2004) Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: A streamlined genome overrun by mobile genetic elements. PLoS Biol. 2, E69
61. Ogata H., Renesto P., Audic S., Robert C., Blanc G., Fournier P. E., Parinello H., Claverie J. M., Raoult D., Galvao M. A., Mafra C., Chamone C. B., Calic S. B., Zavala-Velazquez J. E., Walker D. H., Kelly P. J., Meads N., Theobald A., Fang R., Houhamdi L., Azad A. F., Parola P., Sanogo O. Y., Lerdthusnee K., Zeaiter Z., Chauvancy G., Gonzalez J. P., Miller R. S., Telford S. R., 3rd, Wongsrichanalai C., McDaniel P., Rolain J. M., Franc M., Davoust B., La Scola B., Meconi S., Fenollar F., Roux V., Stuhl L., Maurin M., Richter J., Petridou J., Haussinger D, Enea M. and de Lamballerie X. (2005) The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid in an obligate intracellular parasite. PLoS Biol. 3, e248
62. Batrukova M. A., Betin V. L., Rubtsov A. M. and Lopina O. D. (2000) Ankyrin: structure, properties, and functions. Biochemistry (Mosc) 65, 395 - 408
63. Hryniewicz-Jankowska A., Czogalla A., Bok E. and Sikorsk A. F. (2002) Ankyrins, multifunctional proteins involved in many cellular pathways. Folia Histochem. Cytobiol. 40, 239 - 249
64. Reiss U., Oskouian B., Zhou J., Gupta V., Sooriyakumaran P., Kelly S., Wang E., Merrill A. H. J. and Saba J. D. (2004) Sphingosine-phosphate lyase enhances stress-induced ceramide generation and apoptosis. J. Biol. Chem. 279, 1281-1290
65. Amer A. O. and Swanson M. S. (2005) Autophagy is an immediate macrophage response to Legionella pneumophila. Cell. Microbiol. 7, 765 - 778
66. Biederbick A., Rose S. and Elsasser H. P. (1999) A human intracellular apyrase-like protein, LALP70, localizes to lysosomal/autophagic vacuoles. J. Cell Sci. 112, 2473 - 2484
67. Sansom F. M., Newton H. J. and Hartland E. L. (2006) Eukaryotic-like proteins of Legionella pneumophila as potential virulence factors. ASM Press, Chicago
68. Hakansson S., Galyov E. E., Rosqvist R. and Wolf-Watz H. (1996) The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol. Microbiol. 20, 593-603
69. Barz C., Abahji T. N., Trulzsch K. and Heesemann J. (2000) The Yersinia Ser/Thr protein kinase YpkA/YopO directly interacts with the small GTPases RhoA and Rac-1. FEBS Lett. 482, 139 - 143
70. Walburger A., Koul A., Ferrari G., Nguyen L., Prescianotto-Baschong C., Huygen K., Klebl B., Thompson C., Bacher G. and Pieters J. (2004) Protein kinase G from pathogenic Mycobacteria promotes survival within macrophages. Science 304, 1800 - 1804
71. Vance R. E., Hong S., Gronert K., Serhan C. N. and J. J., Mekalanos. (2004) The opportunistic pathogen Pseudomonas aeruginosa carries a secretable arachidonate 15-lipoxygenase. Proc. Natl. Acad. Sci. USA 101, 2135 - 2139
72. Stebbins C. E. and Galan J. E. (2001) Structural mimicry in bacterial virulence. Nature 412, 701 - 705
73. Rossier O. and Cianciotto N. P. (2005) The Legionella pneumophila tatB gene facilitates secretion of phospholipase C, growth under iron-limiting conditions, and intracellular infection. Infect. Immun. 73, 2020 - 2032
74. De Buck E., Maes L., Meyen E., Van Mellaert L., Geukens N., Anne J. and Lammertyn E. (2005) Legionella pneumophila Philadelphia-1 tatB and tatC affect intracellular replication and biofilm formation. Biochem. Biophys. Res. Commun. 331, 1413 - 1420
75. Jacobi S. and Heuner K. (2003) Description of a putative type I secretion system in Legionella pneumophila. Int. J. Med. Microbiol. 293, 349 - 358
76. Rossier O. and Cianciotto N. P. (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
77. Soderberg M. A., Rossier O. and Cianciotto N. P. (2004) The type II protein secretion system of Legionella pneumophila promotes growth at low temperatures. J. Bacteriol. 186, 3712 - 3720
78. Marra A., Blander S. J., Horwitz M. A. and Shuman H. A. (1992) Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl. Acad. Sci. USA 89, 9607 - 9611
79. Berger K. H. and Isberg R. R. (1993) Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol. Microbiol. 7, 7 - 19
80. Segal G. and Shuman H. A. (1998) Intracellular multiplication and human macrophage killing by Legionella pneumophila are inhibited by conjugal components of IncQ plasmid RSF1010. Mol. Microbiol. 30, 197 - 208
81. Segal G. and Shuman H. A. (1997) Characterization of a new region required for macrophage killing by Legionella pneumophila. Infect. Immun. 65, 5057 - 5066
82. Vogel J. P., Andrews H. L., Wong S. K. and Isberg R. R. (1998) Conjugative transfer by the virulence system of Legionella pneumophila. Science 279, 873 - 876
83. Nagai H. and Roy C. R. (2003) Show me the substrates: modulation of host cell function by type IV secretion systems. Cell. Microbiol. 5, 373 - 383
84. Morozova I., Qu X., Shi S., Asamani G., Greenberg J. E., Shuman H. A. and Russo J. J. (2004) Comparative sequence analysis of the icm/dot genes in Legionella. Plasmid 51, 127 - 147
85. Feldman M. and Segal G. (2004) A specific genomic location within the icm/dot pathogenesis region of different Legionella species encodes functionally similar but nonhomologous virulence proteins. Infect. Immun. 72, 4503-4511
86. Dumenil G. and Isberg R. R. (2001) The Legionella pneumophila IcmR protein exhibits chaperone activity for IcmQ by preventing its participation in high-molecular-weight complexes. Mol. Microbiol. 40, 1113 - 1127
87. Feldman M., Zusman T., Hagag S. and Segal G. (2005) Coevolution between nonhomologous but functionally similar proteins and their conserved partners in the Legionella pathogenesis system. Proc. Natl. Acad. Sci. USA 102, 12206 - 12211
88. Edelstein P. H., Edelstein M. A., Higa F. and Falkow S. (1999) Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model. Proc. Natl. Acad. Sci. USA 96, 8190 - 8195
89. Segal G. and Shuman H. A. (1999) Legionella pneumophila utilizes the same genes to multiply within Acanthamoeba castellanii and human macrophages. Infect. Immun. 67, 2117 - 2124
90. Andrews H. L., Vogel J. P. and Isberg R. R. (1998) Identification of linked Legionella pneumophila genes essential for intracellular growth and evasion of the endocytic pathway. Infect. Immun. 66, 950 - 958
91. Segal G. and Shuman H. A. (1999) Possible origin of the Legionella pneumophila virulence genes and their relation to Coxiella burnetii. Mol. Microbiol. 33, 669 - 670
92. Abu-Zant A., Jones S., Asare R., Suttles J., Price C., Graham J. and Kwaik Y. A. (2006) Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila. Cell. Microbiol. (Epub ahead of print)
93. Nagai H., Kagan J. C., Zhu X., Kahn R. A. and Roy C. R. (2002) A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 295, 679 - 682
94. Nagai H., Cambronne E. D., Kagan J. C., Amor J. C., Kahn R. A. and Roy C. R. (2005) A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc. Natl. Acad. Sci. USA 102, 826 - 831
95. Segal G., Russo J. J. and Shuman H. A. (1999) Relationships between a new type IV secretion system and the icm/dot virulence system of Legionella pneumophila. Mol. Microbiol. 34, 799 - 809
96. Ridenour D. A., Cirillo S. L., Feng S., Samrakandi M. M. and Cirillo J. D. (2003) Identification of a gene that affects the efficiency of host cell infection by Legionella pneumophila in a temperature-dependent fashion. Infect. Immun. 71, 6256 - 6263
97. Doléans-Jordheim A., Akermi M., Ginevra C., Cazalet C., Kay E., Schneider D., Buchrieser C., Atlan D., Vandenesch F., Etienne J. and Jarraud S. (2006) Growth phase-dependent mobility of the lvh-encoding region in Legionella strain Paris. Microbiology (in press)
98. Desvaux M., Parham N. J. and Henderson I. R. (2004) The autotransporter secretion system. Res. Microbiol. 155, 53 - 60
99. Benz I. and Schmidt M. A. (1992) AIDA-I, the adhesin involved in diffuse adherence of the diarrhoeagenic Escherichia coli strain 2787 (O126:H27), is synthesized via a precursor molecule. Mol. Microbiol. 6, 1539 - 1546
100. Klemm P., Hjerrild L., Gjermansen M. and Schembri M. A. (2004) Structure-function analysis of the self-recognizing Antigen 43 autotransporter protein from Escherichia coli. Mol. Microbiol. 51, 283 - 296
101. Payne N. R. and Horwitz M. A. (1987) Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J. Exp. Med. 166, 1377 - 1389
102. Bellinger-Kawahara C. and Horwitz M. A. (1990) Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes. J. Exp. Med. 172, 1201 - 1210
103. Gibson F. C. 3rd, Tzianabos A. O. and Rodgers F. G. (1994) Adherence of Legionella pneumophila to U-937 cells, guinea-pig alveolar macrophages, and MRC-5 cells by a novel, complement-independent binding mechanism. Can. J. Microbiol. 40, 865 - 872
104. Stone B. J. and Abu Kwaik Y. (1998) Expression of multiple pili by Legionella pneumophila: identification and characterization of a type IV pilin gene and its role in adherence to mammalian and protozoan cells. Infect. Immun. 66, 1768 - 1775
105. Garduno R. A., Garduno E. and Hoffman P. S. (1998) Surface-associated hsp60 chaperonin of Legionella pneumophila mediates invasion in a HeLa cell model. Infect. Immun. 66, 4602 - 4610
106. Fettes P. S., Susa M., Hacker J. and Marre R. (2000) Characterization of the Legionella pneumophila gene ligA. Int. J. Med. Microbiol. 290, 239 - 250
107. Helbig J. H., Konig B., Knospe H., Bubert B., Yu C., Luck C. P., Riboldi-Tunnicliffe A., Hilgenfeld R., Jacobs E., Hacker J. and Fischer G. (2003) The PPIase active site of Legionella pneumophila Mip protein is involved in the infection of eukaryotic host cells. Biol. Chem. 384, 125 - 137
108. Helbig J. H., Luck P. C., Steinert M., Jacobs E. and Witt M. (2001) Immunolocalization of the Mip protein of intracellularly and extracellularly grown Legionella pneumophila. Lett. Appl. Microbiol. 32, 83 - 88
109. Kohler R., Fanghanel J., Konig B., Luneberg E., Frosch M., Rahfeld, J. U., Hilgenfeld R., Fischer G., Hacker J. and Steinert M. (2003) Biochemical and functional analyses of the Mip protein: influence of the N-terminal half and of peptidylprolyl isomerase activity on the virulence of Legionella pneumophila. Infect. Immun. 71, 4389 - 4397
110. Cianciotto N. P. (2001) Pathogenicity of Legionella pneumophila. Int. J. Med. Microbiol. 291, 331 - 343
111. Wintermeyer E., Ludwig B., Steinert M., Schmidt B., Fischer G. and Hacker J. (1995) Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells. Infect. Immun. 63, 4576 - 4583
112. Debroy S., Aragon V., Kurtz S. and Cianciotto N. P. (2006) Legionella pneumophila Mip, a surface-exposed peptidylproline cis-trans-isomerase, promotes the presence of phospholipase C-like activity in culture supernatants. Infect. Immun. 74, 5151 - 5160
113. Wagner C., Khan A. S., Kamphausen T., Schmausser B., Ünal C., Lorenz U., Fischer G., Hacker J. and Steinert M. (2006) Collagen binding protein Mip enables Legionella pneumophila to transmigrate through a barrier of NCI-H292 lung epithelial cells and extracellular matrix. Cell. Microbiol. doi:10. 1111/j. 1462-5822. 2006. 00802. x
114. Conover G. M., Derre I., Vogel J. P. and Isberg R. R. (2003) The Legionella pneumophila LidA protein: a translocated substrate of the Dot/Icm system associated with maintenance of bacterial integrity. Mol. Microbiol. 48, 305 - 321
115. Chen J., de Felipe K. S., Clarke M., Lu H., Anderson O. R., Segal G. and Shuman H. A. (2004). Legionella effectors that promote nonlytic release from protozoa. Science 303, 1358 - 1361
116. Luo Z. Q. and Isberg R. R. (2004) Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc. Natl. Acad. Sci. USA 101, 841 - 846
117. Machner M. P. and Isberg R. R. (2006) Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev. Cell 11, 47 - 56
118. Murata T., Delprato A., Ingmundson A., Toomre D. K., Lambright D. G. and Roy C. R. (2006) The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell. Biol. 8, 971 - 977
119. Weber S. S., Ragaz C., Reus K., Nyfeler Y. and Hilbi H. (2006). Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog. 2, e46
120. Shohdy N., Efe J. A., Emr S. D. and Shuman H. A. (2005) Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking. Proc. Natl. Acad. Sci. USA 102, 4866 - 4871
121. Campodonico E. M., Chesnel L. and Roy C. R. (2005) A yeast genetic system for the identification and characterization of substrate proteins transferred into host cells by the Legionella pneumophila Dot/Icm system. Mol. Microbiol. 56, 918 - 933
122. Ninio S., Zuckman-Cholon D. M., Cambronne E. D. and Roy C. R. (2005) The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation. Mol. Microbiol. 55, 912 - 926
123. Fernandez-Moreira E., Helbig J. H. and Swanson M. S. (2006) Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes. Infect. Immun. 74, 3285 - 3295
124. Aragon V., Kurtz S. and Cianciotto N. P. (2001) Legionella pneumophila major acid phosphatase and its role in intracellular infection. Infect. Immun. 69, 177 - 185
125. Aragon V., Kurtz S., Flieger A., Neumeister B. and Cianciotto N. P. (2000) Secreted enzymatic activities of wild-type and pilD-deficient Legionella pneumophila. Infect. Immun. 68, 1855 - 1863
126. Hales L. M. and Shuman H. A. (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
127. Flieger A., Neumeister B. and Cianciotto N. P. (2002) Characterization of the gene encoding the major secreted lysophospholipase A of Legionella pneumophila and its role in detoxification of lysophosphatidylcholine. Infect. Immun. 70, 6094 - 6106
128. Banerji S., Bewersdorff M., Hermes B., Cianciotto N. P. and Flieger A. (2005) Characterization of the major secreted zinc metalloprotease-dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila. Infect. Immun. 73, 2899 - 2909
129. Farris M., Grant A., Richardson T. B. and O'Connor C. D. (1998) BipA: a tyrosine-phosphorylated GTPase that mediates interactions between enteropathogenic Escherichia coli (EPEC) and epithelial cells. Mol. Microbiol. 28, 265 - 279
130. Grant A. J., Farris M., Alefounder P., Williams P. H., Woodward M. J. and O'Connor C. D. (2003) Co-ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic Escherichia coli (EPEC). Mol. Microbiol. 48, 507 - 521
131. Carsiotis M., Stocker B. A., Weinstein D. L. and O'Brien A. D. (1989) A Salmonella typhimurium virulence gene linked to flg. Infect. Immun. 57, 3276 - 3280
132. Rudnick P. A., Arcondeguy T., Kennedy C. K. and Kahn D. (2001) glnD and mviN are genes of an essential operon in Sinorhizobium meliloti. J. Bacteriol. 183, 2682 - 2685
133. Keane O. M. and Dorman C. J. (2003) The gyr genes of Salmonella enterica serovar Typhimurium are repressed by the factor for inversion stimulation, Fis. Mol. Genet. Genomics 270, 56 - 65
134. Kelly A., Goldberg M. D., Carroll R. K., Danino V., Hinton J. C. and Dorman C. J. (2004) A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium. Microbiology 150, 2037 - 2053
135. Osuna R., Lienau D., Hughes K. T. and Johnson R. C. (1995) Sequence, regulation, and functions of fis in Salmonella typhimurium. J. Bacteriol. 177, 2021 - 2032
136. Sheikh J., Hicks S., Dall'Agnol M., Phillips A. D. and Nataro J. P. (2001) Roles for Fis and YafK in biofilm formation by enteroaggregative Escherichia coli. Mol. Microbiol. 41, 983 - 997
137. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S., Barry C. E., 3rd, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R., Devlin K., Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L., Oliver K., Osborne J., Quail M. A., Rajandream M. A., Rogers J., Rutter S., Seeger K., Skelton J., Squares R., Squares S., Sulston J. E., Taylor K., Whitehead S. and Barrell B. G. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537 - 544