ENTRY ko05134 Pathway NAME Legionellosis DESCRIPTION Legionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated with Legionella species: Legionnaires' disease is the more severe form of the infection, which may involve pneumonia, and Pontiac fever is a milder respiratory illness. The pathogenesis of L. pneumophila is derived from its growth within lung macrophages. One of the L. pneumophila's type IV secretion systems, the Dot/Icm secretion system, is of critical importance for its ability to replicate and to cause disease. The Dot/Icm substrates modulate multiple host cell processes and in particular, redirect trafficking of the L. pneumophila phagosome and mediate its conversion into an ER-derived organelle competent for intracellular bacterial replication. L. pneumophila also manipulates host cell death and survival pathways in a way that allows continued intracellular replication. CLASS Human Diseases; Infectious disease: bacterial PATHWAY_MAP ko05134 Legionellosis DISEASE H00311 Legionellosis ORTHOLOGY K15473 effector protein SdeA K11022 structural toxin protein (hemagglutinin/hemolysin) RtxA K15474 enhanced entry protein EnhC K15475 enhanced entry protein LpnE K03197 type IV secretion system protein VirB2 K04077 chaperonin GroEL [EC:5.6.1.7] K03990 complement component 3 K04011 complement component (3b/4b) receptor 1 K06461 integrin alpha M K06464 integrin beta 2 K15476 VPS inhibitor protein A K15477 VPS inhibitor protein D K15478 VPS inhibitor protein E K15479 guanine nucleotide exchange protein RalF K07937 ADP-ribosylation factor 1/2 K15480 effector protein DrrA/SidM [EC:2.7.7.108] K07874 Ras-related protein Rab-1A K07875 Ras-related protein Rab-1B K15481 effector protein LidA K15482 effector protein SidC K15483 effector protein SdcA K08517 vesicle transport protein SEC22 K07953 GTP-binding protein SAR1 [EC:3.6.5.-] K13525 transitional endoplasmic reticulum ATPase K02084 apoptotic protease-activating factor K08738 cytochrome c K04399 caspase 9 [EC:3.4.22.62] K02187 caspase 3 [EC:3.4.22.56] K04398 caspase 8 [EC:3.4.22.61] K00239 succinate dehydrogenase flavoprotein subunit [EC:1.3.5.1] K15484 inhibitor of growth protein SidF K15464 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 K15485 Bcl-2-like protein 13 K15486 serine/threonine-protein kinase LegK1 [EC:2.7.1.-] K04469 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 K04734 NF-kappa-B inhibitor alpha K02580 nuclear factor NF-kappa-B p105 subunit K04735 transcription factor p65 K15487 effector protein SdbA K15488 E3 ubiquitin-protein ligase LubX K23561 dual specificity protein kinase CLK1/4 [EC:2.7.12.1] K15490 glucosyltransferase Lgt1/2/3 K14416 elongation factor 1 alpha-like protein K15491 effector protein SidI K03231 elongation factor 1-alpha K09414 heat shock transcription factor 1 K03283 heat shock 70kDa protein 1/6/8 K03233 elongation factor 1-gamma K03596 GTP-binding protein LepA K15492 effector protein B K02406 flagellin K12807 baculoviral IAP repeat-containing protein 1 K04397 caspase 7 [EC:3.4.22.60] K12805 NLR family CARD domain-containing protein 4 K12799 apoptosis-associated speck-like protein containing a CARD K01370 caspase 1 [EC:3.4.22.36] K05482 interleukin 18 K04519 interleukin 1 beta K10168 toll-like receptor 5 K10159 toll-like receptor 2 K04391 monocyte differentiation antigen CD14 K10160 toll-like receptor 4 K04729 myeloid differentiation primary response protein MyD88 K03156 tumor necrosis factor superfamily, member 2 K05405 interleukin 6 K05406 interleukin 12A K05425 interleukin 12B K10030 interleukin 8 K05505 C-X-C motif chemokine 1/2/3 COMPOUND C00338 Lipopolysaccharide C01277 1-Phosphatidyl-1D-myo-inositol 4-phosphate REFERENCE PMID:20375353 AUTHORS Newton HJ, Ang DK, van Driel IR, Hartland EL TITLE Molecular pathogenesis of infections caused by Legionella pneumophila. JOURNAL Clin Microbiol Rev 23:274-98 (2010) DOI:10.1128/CMR.00052-09 REFERENCE PMID:18363881 AUTHORS Shin S, Roy CR TITLE Host cell processes that influence the intracellular survival of Legionella pneumophila. JOURNAL Cell Microbiol 10:1209-20 (2008) DOI:10.1111/j.1462-5822.2008.01145.x REFERENCE PMID:19157961 AUTHORS Ensminger AW, Isberg RR TITLE Legionella pneumophila Dot/Icm translocated substrates: a sum of parts. JOURNAL Curr Opin Microbiol 12:67-73 (2009) DOI:10.1016/j.mib.2008.12.004 REFERENCE PMID:15972519 AUTHORS Chang B, Kura F, Amemura-Maekawa J, Koizumi N, Watanabe H TITLE Identification of a novel adhesion molecule involved in the virulence of Legionella pneumophila. JOURNAL Infect Immun 73:4272-80 (2005) DOI:10.1128/IAI.73.7.4272-4280.2005 REFERENCE PMID:18549456 AUTHORS Liu M, Conover GM, Isberg RR TITLE Legionella pneumophila EnhC is required for efficient replication in tumour necrosis factor alpha-stimulated macrophages. JOURNAL Cell Microbiol 10:1906-23 (2008) DOI:10.1111/j.1462-5822.2008.01180.x REFERENCE PMID:19021631 AUTHORS Weber SS, Ragaz C, Hilbi H TITLE The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. JOURNAL Cell Microbiol 11:442-60 (2009) DOI:10.1111/j.1462-5822.2008.01266.x REFERENCE PMID:16495539 AUTHORS Newton HJ, Sansom FM, Bennett-Wood V, Hartland EL TITLE Identification of Legionella pneumophila-specific genes by genomic subtractive hybridization with Legionella micdadei and identification of lpnE, a gene required for efficient host cell entry. JOURNAL Infect Immun 74:1683-91 (2006) DOI:10.1128/IAI.74.3.1683-1691.2006 REFERENCE PMID:18048909 AUTHORS De Buck E, Anne J, Lammertyn E TITLE The role of protein secretion systems in the virulence of the intracellular pathogen Legionella pneumophila. JOURNAL Microbiology 153:3948-53 (2007) DOI:10.1099/mic.0.2007/012039-0 REFERENCE PMID:19687203 AUTHORS Chong A, Lima CA, Allan DS, Nasrallah GK, Garduno RA TITLE The purified and recombinant Legionella pneumophila chaperonin alters mitochondrial trafficking and microfilament organization. JOURNAL Infect Immun 77:4724-39 (2009) DOI:10.1128/IAI.00150-09 REFERENCE PMID:1721820 AUTHORS Cooper NR TITLE Complement evasion strategies of microorganisms. JOURNAL Immunol Today 12:327-31 (1991) DOI:10.1016/0167-5699(91)90010-Q REFERENCE PMID:16824952 AUTHORS Machner MP, Isberg RR TITLE Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. JOURNAL Dev Cell 11:47-56 (2006) DOI:10.1016/j.devcel.2006.05.013 REFERENCE PMID:12427954 AUTHORS Neumeister B, Faigle M, Lauber K, Northoff H, Wesselborg S TITLE Legionella pneumophila induces apoptosis via the mitochondrial death pathway. JOURNAL Microbiology 148:3639-50 (2002) DOI:10.1099/00221287-148-11-3639 REFERENCE PMID:17124169 AUTHORS Laguna RK, Creasey EA, Li Z, Valtz N, Isberg RR TITLE A Legionella pneumophila-translocated substrate that is required for growth within macrophages and protection from host cell death. JOURNAL Proc Natl Acad Sci U S A 103:18745-50 (2006) DOI:10.1073/pnas.0609012103 REFERENCE PMID:19666608 AUTHORS Ge J, Xu H, Li T, Zhou Y, Zhang Z, Li S, Liu L, Shao F TITLE A Legionella type IV effector activates the NF-kappaB pathway by phosphorylating the IkappaB family of inhibitors. JOURNAL Proc Natl Acad Sci U S A 106:13725-30 (2009) DOI:10.1073/pnas.0907200106 REFERENCE PMID:18284575 AUTHORS Kubori T, Hyakutake A, Nagai H TITLE Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. JOURNAL Mol Microbiol 67:1307-19 (2008) DOI:10.1111/j.1365-2958.2008.06124.x REFERENCE PMID:19386084 AUTHORS Shen X, Banga S, Liu Y, Xu L, Gao P, Shamovsky I, Nudler E, Luo ZQ TITLE Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of protein synthesis and induction of host stress response. JOURNAL Cell Microbiol 11:911-26 (2009) DOI:10.1111/j.1462-5822.2009.01301.x REFERENCE PMID:19478083 AUTHORS Belyi Y, Stahl M, Sovkova I, Kaden P, Luy B, Aktories K TITLE Region of elongation factor 1A1 involved in substrate recognition by Legionella pneumophila glucosyltransferase Lgt1: identification of Lgt1 as a retaining glucosyltransferase. JOURNAL J Biol Chem 284:20167-74 (2009) DOI:10.1074/jbc.M109.008441 REFERENCE PMID:18281405 AUTHORS Belyi Y, Tabakova I, Stahl M, Aktories K TITLE Lgt: a family of cytotoxic glucosyltransferases produced by Legionella pneumophila. JOURNAL J Bacteriol 190:3026-35 (2008) DOI:10.1128/JB.01798-07 REFERENCE PMID:19343209 AUTHORS Akhter A, Gavrilin MA, Frantz L, Washington S, Ditty C, Limoli D, Day C, Sarkar A, Newland C, Butchar J, Marsh CB, Wewers MD, Tridandapani S, Kanneganti TD, Amer AO TITLE Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection. JOURNAL PLoS Pathog 5:e1000361 (2009) DOI:10.1371/journal.ppat.1000361 REFERENCE PMID:20941588 AUTHORS Palusinska-Szysz M, Janczarek M TITLE Innate immunity to Legionella and toll-like receptors - review. JOURNAL Folia Microbiol (Praha) 55:508-14 (2010) DOI:10.1007/s12223-010-0084-8 REL_PATHWAY ko04210 Apoptosis ko04610 Complement and coagulation cascades ko04620 Toll-like receptor signaling pathway ///