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 K00239 sdhA, frdA; succinate dehydrogenase flavoprotein subunit [EC:1.3.5.1] K01370 CASP1; caspase 1 [EC:3.4.22.36] K02084 APAF1; apoptotic protease-activating factor K02187 CASP3; caspase 3 [EC:3.4.22.56] K02406 fliC, hag; flagellin K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2 K03197 virB2, lvhB2; type IV secretion system protein VirB2 K03231 EEF1A; elongation factor 1-alpha K03233 EEF1G; elongation factor 1-gamma K03283 HSPA1_6_8; heat shock 70kDa protein 1/6/8 K03596 lepA; GTP-binding protein LepA K03990 C3; complement component 3 K04011 CR1, CD35; complement component (3b/4b) receptor 1 K04077 groEL, HSPD1, HSP60, CPN60, ths; chaperonin GroEL [EC:5.6.1.7] K04391 CD14; monocyte differentiation antigen CD14 K04397 CASP7; caspase 7 [EC:3.4.22.60] K04398 CASP8; caspase 8 [EC:3.4.22.61] K04399 CASP9; caspase 9 [EC:3.4.22.62] K04469 NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 K04519 IL1B; interleukin 1 beta K04729 MYD88; myeloid differentiation primary response protein MyD88 K04734 NFKBIA; NF-kappa-B inhibitor alpha K04735 RELA; transcription factor p65 K05405 IL6; interleukin 6 K05406 IL12A; interleukin 12A K05425 IL12B; interleukin 12B K05482 IL18, IL1F4; interleukin 18 K05505 CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3 K06461 ITGAM, CD11b; integrin alpha M K06464 ITGB2, CD18; integrin beta 2 K07874 RAB1A; Ras-related protein Rab-1A K07875 RAB1B; Ras-related protein Rab-1B K07937 ARF1_2; ADP-ribosylation factor 1/2 K07953 SAR1; GTP-binding protein SAR1 [EC:3.6.5.-] K08517 SEC22; vesicle transport protein SEC22 K08738 CYC; cytochrome c K09414 HSF1; heat shock transcription factor 1 K10030 IL8, CXCL8; interleukin 8 K10159 TLR2, CD282; toll-like receptor 2 K10160 TLR4, CD284; toll-like receptor 4 K10168 TLR5; toll-like receptor 5 K11022 rtxA1, rtxA; structural toxin protein (hemagglutinin/hemolysin) RtxA K12799 PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD K12805 NLRC4, CARD12; NLR family CARD domain-containing protein 4 K12807 NAIP, BIRC1; baculoviral IAP repeat-containing protein 1 K13525 VCP, CDC48; transitional endoplasmic reticulum ATPase K14416 HBS1; elongation factor 1 alpha-like protein K15464 BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 K15473 sdeA, laiA; effector protein SdeA K15474 enhC; enhanced entry protein EnhC K15475 lpnE; enhanced entry protein LpnE K15476 vipA; VPS inhibitor protein A K15477 vipD; VPS inhibitor protein D K15478 vipE; VPS inhibitor protein E K15479 ralF; guanine nucleotide exchange protein RalF K15480 drrA, sidM; effector protein DrrA/SidM [EC:2.7.7.108] K15481 lidA; effector protein LidA K15482 sidC; effector protein SidC K15483 sdcA; effector protein SdcA K15484 sidF; inhibitor of growth protein SidF K15485 BCL2L13, BCL-RAMBO; Bcl-2-like protein 13 K15486 legK1; serine/threonine-protein kinase LegK1 [EC:2.7.1.-] K15487 sdbA; effector protein SdbA K15488 lubX; E3 ubiquitin-protein ligase LubX K15490 lgt1_2_3; glucosyltransferase Lgt1/2/3 K15491 sidI; effector protein SidI K15492 K15492, lepB; effector protein B K23561 CLK1_4; dual specificity protein kinase CLK1/4 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 ///