KEGG PATHWAY: ko05134

PATHWAY: ko05134

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; 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