Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway

PLoS Pathogens

Volumn 11, Issue 12, 2015, Pages

  Simon, Sylvia ^a,b   Schell, Ursula ^a   Heuer, Natalie ^c   Hager, Dominik ^a   Albers, Michael F ^d   Matthias, Jan ^c   Fahrnbauer, Felix ^a   Trauner, Dirk ^a   Eichinger, Ludwig ^c   Hedberg, Christian ^d,e   Hilbi, Hubert ^a,b  

^a UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY OF ZURICH   (Switzerland)

^c UNIVERSITY OF COLOGNE   (Germany)

^d UMEÅ UNIVERSITY   (Sweden)

^e MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYTRIDECANE 4 ONE; CARBOXYLIC ACID DERIVATIVE; IQ MOTIF CONTAINING GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN 1; PROTEIN CDC42; RAC1 PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; SCAFFOLD PROTEIN; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ARHGEF9 PROTEIN, HUMAN; BACTERIAL PROTEIN; GAMMA BUTYROLACTONE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; N-(3-OXOHEXANOYL)-3-AMINODIHYDRO-2(3H)-FURANONE; RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR;

A549 CELL LINE; ANIMAL CELL; ARTICLE; CELL MIGRATION; CONFOCAL LASER MICROSCOPY; CONTROLLED STUDY; CYTOTOXICITY ASSAY; DICTYOSTELIUM DISCOIDEUM; GENE EXPRESSION REGULATION; HOST PATHOGEN INTERACTION; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE MICROSCOPY; INTRACELLULAR SIGNALING; LEGIONELLA PNEUMOPHILA; LEGIONNAIRE DISEASE; MACROPHAGE; MICROARRAY ANALYSIS; MIGRATION INHIBITION; NONHUMAN; PROTEIN PHOSPHORYLATION; QUORUM SENSING; REAL TIME POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SYNTHESIS; UPTAKE ASSAY; WESTERN BLOTTING; ANALOGS AND DERIVATIVES; ANIMAL; CELL LINE; CELL MOTION; FLUORESCENCE MICROSCOPY; GENETIC TRANSFECTION; HOST PARASITE INTERACTION; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

4-BUTYROLACTONE; ANIMALS; BACTERIAL PROTEINS; BLOTTING, WESTERN; CDC42 GTP-BINDING PROTEIN; CELL LINE; CELL MOVEMENT; HOST-PARASITE INTERACTIONS; LEGIONELLA PNEUMOPHILA; LEGIONNAIRES' DISEASE; MICROSCOPY, FLUORESCENCE; QUORUM SENSING; RAS GTPASE-ACTIVATING PROTEINS; REAL-TIME POLYMERASE CHAIN REACTION; RHO GUANINE NUCLEOTIDE EXCHANGE FACTORS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRANSFECTION;

EID: 84953321712     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005307     Document Type: Article

References (64)

1. Ng WL, Bassler BL, Bacterial quorum-sensing network architectures. Annual review of genetics. 2009;43:197–222. Epub 2009/08/19. doi: 10.1146/annurev-genet-102108-134304 19686078.
2. Shank EA, Kolter R, New developments in microbial interspecies signaling. Current opinions in microbiology 2009;12(2):205–14. Epub 2009/03/03. doi: 10.1016/j.mib.2009.01.003 19251475.
3. Tiaden A, Spirig T, Hilbi H, Bacterial gene regulation by α-hydroxyketone signaling. Trends in microbiology 2010;18(7):288–97. Epub 2010/04/13. doi: 10.1016/j.tim.2010.03.004 20382022.
4. Tiaden A, Hilbi H, α-Hydroxyketone synthesis and sensing by Legionella and Vibrio. Sensors. 2012;12(3):2899–919. Epub 2012/03/02. doi: 10.3390/s120302899 22736983.
5. Winans SC, A new family of quorum sensing pheromones synthesized using S-adenosylmethionine and Acyl-CoAs. Molecular microbiology. 2011;79(6):1403–6. Epub 2011/03/11. doi: 10.1111/j.1365-2958.2011.07551.x 21388458.
6. Higgins DA, Pomianek ME, Kraml CM, Taylor RK, Semmelhack MF, Bassler BL, The major Vibrio cholerae autoinducer and its role in virulence factor production. Nature. 2007;450(7171):883–6. Epub 2007/11/16. doi: 10.1038/nature06284 18004304.
7. Spirig T, Tiaden A, Kiefer P, Buchrieser C, Vorholt JA, Hilbi H, The Legionella autoinducer synthase LqsA produces an α-hydroxyketone signaling molecule. The Journal of biological chemistry. 2008;283(26):18113–23. Epub 2008/04/16. doi: 10.1074/jbc.M801929200 18411263.
8. Hornung C, Poehlein A, Haack FS, Schmidt M, Dierking K, Pohlen A, et al. The Janthinobacterium sp. HH01 genome encodes a homologue of the V. cholerae CqsA and L. pneumophila LqsA autoinducer synthases. PLoS one. 2013;8(2):e55045. Epub 2013/02/14. doi: 10.1371/journal.pone.0055045 23405110.
9. Ke X, Miller LC, Ng WL, Bassler BL, CqsA-CqsS quorum-sensing signal-receptor specificity in Photobacterium angustum. Molecular microbiology. 2014;91(4):821–33. Epub 2014/01/14. doi: 10.1111/mmi.12502 24372841.
10. Tiaden A, Spirig T, Weber SS, Brüggemann H, Bosshard R, Buchrieser C, et al. The Legionella pneumophila response regulator LqsR promotes host cell interactions as an element of the virulence regulatory network controlled by RpoS and LetA. Cellular microbiology 2007;9(12):2903–20. Epub 2007/07/05. 17614967.
11. Sahr T, Rusniok C, Dervins-Ravault D, Sismeiro O, Coppee JY, Buchrieser C, Deep sequencing defines the transcriptional map of L. pneumophila and identifies growth phase-dependent regulated ncRNAs implicated in virulence. RNA biology 2012;9(4). Epub 2012/04/01. doi: 10.4161/rna.20270 22546937.
12. Kessler A, Schell U, Sahr T, Tiaden A, Harrison C, Buchrieser C, et al. The Legionella pneumophila orphan sensor kinase LqsT regulates competence and pathogen-host interactions as a component of the LAI-1 circuit. Environmental microbiology. 2013;15(2):646–62. Epub 2012/10/05. doi: 10.1111/j.1462-2920.2012.02889.x 23033905.
13. Schell U, Kessler A, Hilbi H, Phosphorylation signalling through the Legionella quorum sensing histidine kinases LqsS and LqsT converges on the response regulator LqsR. Molecular microbiology. 2014;92(5):1039–55. Epub 2014/05/06. doi: 10.1111/mmi.12612 24720786.
14. Schell U, Simon S, Sahr T, Hager D, Albers MF, Kessler A, et al. The α-hydroxyketone LAI-1 regulates motility, Lqs-dependent phosphorylation signaling and gene expression of Legionella pneumophila. Molecular microbiology. 2015. Epub ahead of print.
15. Tiaden A, Spirig T, Carranza P, Brüggemann H, Riedel K, Eberl L, et al. Synergistic contribution of the Legionella pneumophila lqs genes to pathogen-host interactions. Journal of bacteriology. 2008;190(22):7532–47. Epub 2008/09/23. doi: 10.1128/JB.01002-08 18805977.
16. Tiaden A, Spirig T, Sahr T, Wälti MA, Boucke K, Buchrieser C, et al. The autoinducer synthase LqsA and putative sensor kinase LqsS regulate phagocyte interactions, extracellular filaments and a genomic island of Legionella pneumophila. Environmental microbiology. 2010;12(5):1243–59. Epub 2010/02/13. doi: 10.1111/j.1462-2920.2010.02167.x 20148929.
17. Newton HJ, Ang DK, van Driel IR, Hartland EL, Molecular pathogenesis of infections caused by Legionella pneumophila. Clinical microbiology reviews. 2010;23(2):274–98. Epub 2010/04/09. doi: 10.1128/CMR.00052-09 20375353.
18. Hilbi H, Hoffmann C, Harrison CF, Legionella spp. outdoors: colonization, communication and persistence. Environmental microbiology reports. 2011;3(3):286–96. Epub 2011/03/21. doi: 10.1111/j.1758-2229.2011.00247.x 23761274.
19. Hubber A, Roy CR, Modulation of host cell function by Legionella pneumophila type IV effectors. Annual review of cell and developmental biology. 2010;26:261–83. Epub 2010/10/12. doi: 10.1146/annurev-cellbio-100109-104034 20929312.
20. Isberg RR, O'Connor TJ, Heidtman M, The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nature reviews Microbiology. 2009;7(1):13–24. Epub 2008/11/18. doi: 10.1038/nrmicro1967 19011659.
21. Hilbi H, Haas A, Secretive bacterial pathogens and the secretory pathway. Traffic. 2012;13(9):1187–97. Epub 2012/02/22. doi: 10.1111/j.1600-0854.2012.01344.x 22340894.
22. Sherwood RK, Roy CR, A Rab-centric perspective of bacterial pathogen-occupied vacuoles. Cell host microbe. 2013;14(3):256–68. Epub 2013/09/17. doi: 10.1016/j.chom.2013.08.010 24034612.
23. Haneburger I, Hilbi H, Phosphoinositide lipids and the Legionella pathogen vacuole. Current topics in microbiology and immunology. 2013;376:155–73. Epub 2013/08/07. doi: 10.1007/82_2013_341 23918172.
24. Finsel I, Hilbi H, Formation of a pathogen vacuole according to Legionella pneumophila: how to kill one bird with many stones. Cellular microbiology. 2015;17(7):935–50. Epub 2015/05/13. doi: 10.1111/cmi.12450 25903720.
25. Simon S, Wagner MA, Rothmeier E, Müller-Taubenberger A, Hilbi H, Icm/Dot-dependent inhibition of phagocyte migration by Legionella is antagonized by a translocated Ran GTPase activator. Cellular microbiology. 2014;16(7):977–92. Epub 2014/01/27. doi: 10.1111/cmi.12258 24397557.
26. Rothmeier E, Pfaffinger G, Hoffmann C, Harrison CF, Grabmayr H, Repnik U, et al. Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection. PLoS pathogens. 2013;9(9):e1003598. Epub 2013/09/27. doi: 10.1371/journal.ppat.1003598 24068924.
27. Jacquemet G, Humphries MJ, IQGAP1 is a key node within the small GTPase network. Small GTPases. 2013;4(4):199–207. Epub 2013/12/19. doi: 10.4161/sgtp.27451 24355937.
28. Wei Y, Perez LJ, Ng WL, Semmelhack MF, Bassler BL, Mechanism of Vibrio cholerae autoinducer-1 biosynthesis. ACS chemical biology. 2011;6(4):356–65. Epub 2011/01/05. doi: 10.1021/cb1003652 21197957.
29. Ng WL, Perez LJ, Wei Y, Kraml C, Semmelhack MF, Bassler BL, Signal production and detection specificity in Vibrio CqsA/CqsS quorum-sensing systems. Molecular microbiology. 2011;79(6):1407–17. Epub 2011/01/12. doi: 10.1111/j.1365-2958.2011.07548.x 21219472.
30. Hoffmann C, Finsel I, Otto A, Pfaffinger G, Rothmeier E, Hecker M, et al. Functional analysis of novel Rab GTPases identified in the proteome of purified Legionella-containing vacuoles from macrophages. Cellular microbiology. 2014;16(7):1034–52. Epub 2014/01/27. doi: 10.1111/cmi.12256 24373249.
31. Brown MD, Sacks DB, IQGAP1 in cellular signaling: bridging the GAP. Trends in cell biology. 2006;16(5):242–9. Epub 2006/04/03. doi: 10.1016/j.tcb.2006.03.002 16595175.
32. White CD, Erdemir HH, Sacks DB, IQGAP1 and its binding proteins control diverse biological functions. Cellular signalling. 2012;24(4):826–34. Epub 2011/12/11. doi: 10.1016/j.cellsig.2011.12.005 22182509.
33. Farbrother P, Wagner C, Na J, Tunggal B, Morio T, Urushihara H, et al. Dictyostelium transcriptional host cell response upon infection with Legionella. Cellular microbiology. 2006;8(3):438–56. 16469056.
34. Urushihara H, Morio T, Saito T, Kohara Y, Koriki E, Ochiai H, et al. Analyses of cDNAs from growth and slug stages of Dictyostelium discoideum. Nucleic acids research. 2004;32(5):1647–53. doi: 10.1093/nar/gkh262 15010511.
35. Srivatsan S, Swiecki M, Otero K, Cella M, Shaw AS, CD2-associated protein regulates plasmacytoid dendritic cell migration, but is dispensable for their development and cytokine production. Journal of immunology. 2013;191(12):5933–40. Epub 2013/11/11. doi: 10.4049/jimmunol.1300454 24218450.
36. Pacheco AR, Sperandio V, Inter-kingdom signaling: chemical language between bacteria and host. Current opinion in microbiology. 2009;12(2):192–8. Epub 2009/03/26. doi: 10.1016/j.mib.2009.01.006 19318290.
37. Bolitho ME, Perez LJ, Koch MJ, Ng WL, Bassler BL, Semmelhack MF, Small molecule probes of the receptor binding site in the Vibrio cholerae CAI-1 quorum sensing circuit. Bioorganic and medicinal chemistry. 2011;19(22):6906–18. Epub 2011/10/18. doi: 10.1016/j.bmc.2011.09.021 22001326.
38. Werner KM, Perez LJ, Ghosh R, Semmelhack MF, Bassler BL, Caenorhabditis elegans recognizes a bacterial quorum-sensing signal molecule through the AWCON neuron. The Journal of biological chemistry. 2014;289(38):26566–73. Epub 2014/08/04. doi: 10.1074/jbc.M114.573832 25092291.
39. Filic V, Marinovic M, Faix J, Weber I, The IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as an effector and a sequestrator of Rac1 GTPases. Cellular and molecular life sciences. 2014;71(15):2775–85. Epub 2014/03/25. doi: 10.1007/s00018-014-1606-3 24664433.
40. Eichinger L, Pachebat JA, Glöckner G, Rajandream MA, Sucgang R, Berriman M, et al. The genome of the social amoeba Dictyostelium discoideum. Nature. 2005;435(7038):43–57. 15875012.
41. Hart MJ, Callow MG, Souza B, Polakis P, IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. The EMBO journal. 1996;15(12):2997–3005. 8670801.
42. Swart-Mataraza JM, Li Z, Sacks DB, IQGAP1 is a component of Cdc42 signaling to the cytoskeleton. The Journal of biological chemistry. 2002;277(27):24753–63. Epub 2002/04/10. doi: 10.1074/jbc.M111165200 11948177.
43. Chen L, Chan TH, Yuan YF, Hu L, Huang J, Ma S, et al. CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients. The Journal of clinical investigations. 2010;120(4):1178–91. Epub 2010/03/24. doi: 10.1172/JCI40665 20335658.
44. Cheng W, Su Y, Xu F, CHD1L: a novel oncogene. Molecular cancer. 2013;12(1):170. doi: 10.1186/1476-4598-12-170 24359616.
45. Brown MD, Bry L, Li Z, Sacks DB, IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42. The Journal of biological chemistry. 2007;282(41):30265–72. Epub 2007/08/11. doi: 10.1074/jbc.M702537200 17693642.
46. Worley MJ, Nieman GS, Geddes K, Heffron F, Salmonella typhimurium disseminates within its host by manipulating the motility of infected cells. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(47):17915–20. Epub 2006/11/11. doi: 10.1073/pnas.0604054103 17095609.
47. McLaughlin LM, Govoni GR, Gerke C, Gopinath S, Peng K, Laidlaw G, et al. The Salmonella SPI2 effector SseI mediates long-term systemic infection by modulating host cell migration. PLoS pathogens. 2009;5(11):e1000671. Epub 2009/12/04. doi: 10.1371/journal.ppat.1000671 19956712.
48. Zhang L, Li X, Wang B, Zhang T, Ye J, Chlamydophila (Chlamydia) pneumoniae infection promotes vascular smooth muscle cell adhesion and migration through IQ domain GTPase-activating protein 1. Microbial pathogenesis. 2012;53(5–6):207–13. Epub 2012/07/28. doi: 10.1016/j.micpath.2012.07.005 22835851.
49. Heymann J, Rejman Lipinski A, Bauer B, Meyer TF, Heuer D, Chlamydia trachomatis infection prevents front-rear polarity of migrating HeLa cells. Cellular microbiology. 2013;15(7):1059–69. Epub 2013/01/29. doi: 10.1111/cmi.12114 23351274.
50. Okude M, Matsuo J, Nakamura S, Kawaguchi K, Hayashi Y, Sakai H, et al. Environmental chlamydiae alter the growth speed and motility of host acanthamoebae. Microbes and environment. 2012;27(4):423–9. Epub 2012/10/27. doi: 10.1264/jsme2.ME11353 23100025.
51. Karlsson T, Turkina MV, Yakymenko O, Magnusson KE, Vikstrom E, The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration. PLoS pathogens. 2012;8(10):e1002953. Epub 2012/10/11. doi: 10.1371/journal.ppat.1002953 23071436.
52. Feeley JC, Gibson RJ, Gorman GW, Langford NC, Rasheed JK, Mackel DC, et al. Charcoal-yeast extract agar: primary isolation medium for Legionella pneumophila. Journal of clinical microbiology. 1979;10(4):437–41. 393713
53. Ragaz C, Pietsch H, Urwyler S, Tiaden A, Weber SS, Hilbi H, The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cellular microbiology. 2008;10(12):2416–33. Epub 2008/08/05. doi: 10.1111/j.1462-5822.2008.01219.x 18673369.
54. Weber SS, Ragaz C, Reus K, Nyfeler Y, Hilbi H, Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS pathogens 2006;2(5):e46. Epub 2006/05/19. 16710455.
55. Weber SS, Ragaz C, Hilbi H, The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. Cellular microbiology. 2009;11(3):442–60. Epub 2008/11/22. doi: 10.1111/j.1462-5822.2008.01266.x 19021631.
56. Brombacher E, Urwyler S, Ragaz C, Weber SS, Kami K, Overduin M, et al. Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila. The Journal of biological chemistry. 2009;284(8):4846–56. Epub 2008/12/20. doi: 10.1074/jbc.M807505200 19095644.
57. Laevsky G, Knecht DA, Under-agarose folate chemotaxis of Dictyostelium discoideum amoebae in permissive and mechanically inhibited conditions. Biotechniques. 2001;31(5):1140–2, 4, 6–9. Epub 2001/12/04. 11730020.
58. Heit B, Kubes P, Measuring chemotaxis and chemokinesis: the under-agarose cell migration assay. Science's signal transduction knowledge environment. 2003;2003(170):PL5. Epub 2003/02/20. doi: 10.1126/stke.2003.170.pl5 12591998.
59. Liang CC, Park AY, Guan JL, In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nature protocols. 2007;2(2):329–33. Epub 2007/04/05. doi: 10.1038/nprot.2007.30 17406593.
60. Na J, Tunggal B, Eichinger L, STATc is a key regulator of the transcriptional response to hyperosmotic shock. BMC genomics. 2007;8:123. doi: 10.1186/1471-2164-8-123 17517120.
61. Tiaden AN, Kessler A, Hilbi H, Analysis of Legionella infection by flow cytometry. Methods in molecular biology. 2013;954:233–49. Epub 2012/11/15. doi: 10.1007/978-1-62703-161-5_14 23150400.
62. Sadosky AB, Wiater LA, Shuman HA, Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infection and immunity. 1993;61(12):5361–73. 8225610
63. Segal G, Shuman HA, Intracellular multiplication and human macrophage killing by Legionella pneumophila are inhibited by conjugal components of IncQ plasmid RSF1010. Molecular microbiology. 1998;30(1):197–208. 9786196
64. Mampel J, Spirig T, Weber SS, Haagensen JAJ, Molin S, Hilbi H, Planktonic replication is essential for biofilm formation by Legionella pneumophila in a complex medium under static and dynamic flow conditions. Applied and environmental microbiology. 2006;72(4):2885–95. 16597995.