KEGG   PATHWAY: hsa05134Help
Entry
hsa05134                    Pathway                                

Name
Legionellosis - Homo sapiens (human)
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 diseases: Bacterial
BRITE hierarchy
Pathway map
hsa05134  Legionellosis
hsa05134

Ortholog table
Disease
H00311  Legionellosis
Organism
Homo sapiens (human) [GN:hsa]
Gene
3329  HSPD1; heat shock protein family D (Hsp60) member 1 [KO:K04077]
718  C3; complement C3 [KO:K03990]
1378  CR1; complement C3b/C4b receptor 1 (Knops blood group) [KO:K04011]
3684  ITGAM; integrin subunit alpha M [KO:K06461]
3689  ITGB2; integrin subunit beta 2 [KO:K06464]
375  ARF1; ADP ribosylation factor 1 [KO:K07937]
5861  RAB1A; RAB1A, member RAS oncogene family [KO:K07874]
81876  RAB1B; RAB1B, member RAS oncogene family [KO:K07875]
9554  SEC22B; SEC22 homolog B, vesicle trafficking protein (gene/pseudogene) [KO:K08517]
56681  SAR1A; secretion associated Ras related GTPase 1A [KO:K07953] [EC:3.6.5.-]
51128  SAR1B; secretion associated Ras related GTPase 1B [KO:K07953] [EC:3.6.5.-]
7415  VCP; valosin containing protein [KO:K13525]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
54205  CYCS; cytochrome c, somatic [KO:K08738]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
664  BNIP3; BCL2 interacting protein 3 [KO:K15464]
23786  BCL2L13; BCL2 like 13 [KO:K15485]
4791  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
10767  HBS1L; HBS1 like translational GTPase [KO:K14416]
1915  EEF1A1; eukaryotic translation elongation factor 1 alpha 1 [KO:K03231]
1917  EEF1A2; eukaryotic translation elongation factor 1 alpha 2 [KO:K03231]
3297  HSF1; heat shock transcription factor 1 [KO:K09414]
3312  HSPA8; heat shock protein family A (Hsp70) member 8 [KO:K03283]
3303  HSPA1A; heat shock protein family A (Hsp70) member 1A [KO:K03283]
3306  HSPA2; heat shock protein family A (Hsp70) member 2 [KO:K03283]
3305  HSPA1L; heat shock protein family A (Hsp70) member 1 like [KO:K03283]
3304  HSPA1B; heat shock protein family A (Hsp70) member 1B [KO:K03283]
3310  HSPA6; heat shock protein family A (Hsp70) member 6 [KO:K03283]
1937  EEF1G; eukaryotic translation elongation factor 1 gamma [KO:K03233]
4671  NAIP; NLR family apoptosis inhibitory protein [KO:K12807]
840  CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
58484  NLRC4; NLR family CARD domain containing 4 [KO:K12805]
29108  PYCARD; PYD and CARD domain containing [KO:K12799]
834  CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36]
3606  IL18; interleukin 18 [KO:K05482]
3553  IL1B; interleukin 1 beta [KO:K04519]
7100  TLR5; toll like receptor 5 [KO:K10168]
7097  TLR2; toll like receptor 2 [KO:K10159]
929  CD14; CD14 molecule [KO:K04391]
7099  TLR4; toll like receptor 4 [KO:K10160]
4615  MYD88; MYD88, innate immune signal transduction adaptor [KO:K04729]
7124  TNF; tumor necrosis factor [KO:K03156]
3569  IL6; interleukin 6 [KO:K05405]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
3576  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
2919  CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505]
2920  CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505]
2921  CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505]
1195  CLK1; CDC like kinase 1 [KO:K08823] [EC:2.7.12.1]
Compound
C00338  Lipopolysaccharide
C01277  1-Phosphatidyl-1D-myo-inositol 4-phosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
KO pathway
ko05134   

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