KEGG PATHWAY: ko05133

PATHWAY: ko05133

Entry

ko05133                     Pathway

Name

Pertussis

Description

Pertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory wheezing and post-tussive vomiting.
Following the inhalation of respiratory secretions from an infected individual, bacteria enter the upper respiratory tract and adhere to epithelial cells. Several adhesion factors have been implicated: the filamentous hemagglutinin (FHA), fimbriae, and pertactin (Prn).
Pertussis toxin (Ptx) and adenylate cyclase toxin (ACT) have been identified so far as major protein toxins of B. pertussis. PTX is a hexameric AB5-type exotoxin. Catalytic A subunit catalyzes the ADP-ribosylation of the Gi subunits of the heterotrimeric G protein, then inhibits multiple downstream pathways. ACT is able to penetrate the cytoplasmic membrane of host cells and becomes activated through the cleavage and the binding of calmodulin (CaM). Activated ACT converts ATP to cyclic AMP and subverts cellular signaling pathways.

Class

Human Diseases; Infectious disease: bacterial

Pathway map

ko05133

Pertussis

Module

M00574

Pertussis pathogenicity signature, pertussis toxin [PATH:ko05133]

M00575

Pertussis pathogenicity signature, T1SS [PATH:ko05133]

Disease

H00319

Pertussis

Orthology

K01330

C1R; complement component 1, r subcomponent [EC:3.4.21.41]

K01331

C1S; complement component 1, s subcomponent [EC:3.4.21.42]

K01332

C2; complement component 2 [EC:3.4.21.43]

K01370

CASP1; caspase 1 [EC:3.4.22.36]

K02183

CALM; calmodulin

K02187

CASP3; caspase 3 [EC:3.4.22.56]

K02580

NFKB1; nuclear factor NF-kappa-B p105 subunit

K03156

TNF, TNFA; tumor necrosis factor superfamily, member 2

K03175

TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]

K03986

C1QA; complement C1q subcomponent subunit A

K03987

C1QB; complement C1q subcomponent subunit B

K03988

C1QG; complement C1q subcomponent subunit C

K03989

C4; complement component 4

K03990

C3; complement component 3

K03994

C5; complement component 5

K04001

SERPING1, C1INH; C1 inhibitor

K04002

C4BPA; complement component 4 binding protein alpha

K04003

C4BPB; complement component 4 binding protein beta

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04379

FOS; proto-oncogene protein c-fos

K04383

IL1A; interleukin 1 alpha

K04391

CD14; monocyte differentiation antigen CD14

K04397

CASP7; caspase 7 [EC:3.4.22.60]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04441

P38; p38 MAP kinase [EC:2.7.11.24]

K04448

JUN; transcription factor AP-1

K04513

RHOA; Ras homolog gene family, member A

K04519

IL1B; interleukin 1 beta

K04630

GNAI; guanine nucleotide-binding protein G(i) subunit alpha

K04729

MYD88; myeloid differentiation primary response protein MyD88

K04730

IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]

K04733

IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]

K04735

RELA; transcription factor p65

K05400

LY96, MD-2; lymphocyte antigen 96

K05403

TIRAP; toll-interleukin 1 receptor (TIR) domain-containing adaptor protein

K05405

IL6; interleukin 6

K05406

IL12A; interleukin 12A

K05409

TIRP, TRAM; TRIF-related adaptor molecule

K05411

IRF3; interferon regulatory factor 3

K05425

IL12B; interleukin 12B

K05426

IL23A; interleukin 23 subunit alpha

K05443

IL10, CSIF; interleukin 10

K05506

CXCL5_6, SCYB5_6; C-X-C motif chemokine 5/6

K05719

ITGB1, CD29; integrin beta 1

K05765

CFL; cofilin

K05842

TRIF; toll-like receptor adapter molecule 1

K06461

ITGAM, CD11b; integrin alpha M

K06464

ITGB2, CD18; integrin beta 2

K06484

ITGA5, CD49e; integrin alpha 5

K07326

fhaC; hemolysin activation/secretion protein

K07345

fimA; major type 1 subunit fimbrin (pilin)

K07347

fimD, fimC, mrkC, htrE, cssD; outer membrane usher protein

K07389

cyaC, hlyC, rtxC; cytolysin-activating lysine-acyltransferase [EC:2.3.1.-]

K07679

evgS, bvgS; two-component system, NarL family, sensor histidine kinase EvgS [EC:2.7.13.3]

K07690

evgA, bvgA; two-component system, NarL family, response regulator EvgA

K08727

NOD1, CARD4; nucleotide-binding oligomerization domain-containing protein 1

K09444

IRF1; interferon regulatory factor 1

K10030

IL8, CXCL8; interleukin 8

K10067

SFTPA; pulmonary surfactant-associated protein A

K10155

IRF8; interferon regulatory factor 8

K10160

TLR4, CD284; toll-like receptor 4

K11003

hlyD, cyaD; membrane fusion protein, hemolysin D

K11004

hlyB, cyaB; ATP-binding cassette, subfamily B, bacterial HlyB/CyaB

K11023

ptxA, artA, pltA; pertussis toxin subunit 1 [EC:2.4.2.-]

K11024

ptxB; pertussis toxin subunit 2

K11025

ptxC; pertussis toxin subunit 3

K11026

ptxD; pertussis toxin subunit 4

K11027

ptxE; pertussis toxin subunit 5

K12340

tolC, bepC, cyaE, raxC, sapF, rsaF, hasF; outer membrane protein

K12681

prn; pertactin

K12683

brkA; serum resistance protein

K12688

sphB1, nalP, ausP; autotransporter serine protease [EC:3.4.21.-]

K12799

PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD

K12800

NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3

K12973

pagP, crcA; lipid IVA palmitoyltransferase [EC:2.3.1.251]

K13241

NOS2; nitric-oxide synthase, inducible [EC:1.14.13.39]

K15125

fhaB; filamentous hemagglutinin

K15126

bteA; type III secretion system cytotoxic effector protein

K22944

cyaA; bifunctional hemolysin/adenylate cyclase

Compound

C00002

ATP

C00076

Calcium cation

C00238

Potassium cation

C00253

Nicotinate

C00338

Lipopolysaccharide

C00374

Heparin

C00575

3',5'-Cyclic AMP

C05005

Glycolipid

C12505

Magnesium sulfate

C19596

Lipooligosaccharide

Reference

PMID:21204863

Authors

de Gouw D, Diavatopoulos DA, Bootsma HJ, Hermans PW, Mooi FR

Title

Pertussis: a matter of immune modulation.

Journal

FEMS Microbiol Rev 35:441-74 (2011)
DOI:10.1111/j.1574-6976.2010.00257.x

Reference

PMID:20210554

Authors

Carbonetti NH

Title

Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools.

Journal

Future Microbiol 5:455-69 (2010)
DOI:10.2217/fmb.09.133

Reference

PMID:10540218

Authors

van den Berg BM, van Furth R, Hazenbos WL

Title

Activation of complement receptor 3 on human monocytes by cross-linking of very-late antigen-5 is mediated via protein tyrosine kinases.

Journal

Immunology 98:197-202 (1999)
DOI:10.1046/j.1365-2567.1999.00871.x

Reference

PMID:16999837

Authors

Mazar J, Cotter PA

Title

Topology and maturation of filamentous haemagglutinin suggest a new model for two-partner secretion.

Journal

Mol Microbiol 62:641-54 (2006)
DOI:10.1111/j.1365-2958.2006.05392.x

Reference

PMID:16390441

Authors

Hewlett EL, Donato GM, Gray MC

Title

Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: more than just making cyclic AMP!

Journal

Mol Microbiol 59:447-59 (2006)
DOI:10.1111/j.1365-2958.2005.04958.x

Reference

PMID:20610650

Authors

Dunne A, Ross PJ, Pospisilova E, Masin J, Meaney A, Sutton CE, Iwakura Y, Tschopp J, Sebo P, Mills KH

Title

Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.

Journal

J Immunol 185:1711-9 (2010)
DOI:10.4049/jimmunol.1000105

Reference

PMID:18401006

Authors

Hickey FB, Brereton CF, Mills KH

Title

Adenylate cycalse toxin of Bordetella pertussis inhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells.

Journal

J Leukoc Biol 84:234-43 (2008)
DOI:10.1189/jlb.0208113

Reference

PMID:16622221

Authors

Spensieri F, Fedele G, Fazio C, Nasso M, Stefanelli P, Mastrantonio P, Ausiello CM

Title

Bordetella pertussis inhibition of interleukin-12 (IL-12) p70 in human monocyte-derived dendritic cells blocks IL-12 p35 through adenylate cyclase toxin-dependent cyclic AMP induction.

Journal

Infect Immun 74:2831-8 (2006)
DOI:10.1128/IAI.74.5.2831-2838.2006

Reference

PMID:17148436

Authors

Fiser R, Masin J, Basler M, Krusek J, Spulakova V, Konopasek I, Sebo P

Title

Third activity of Bordetella adenylate cyclase (AC) toxin-hemolysin. Membrane translocation of AC domain polypeptide promotes calcium influx into CD11b+ monocytes independently of the catalytic and hemolytic activities.

Journal

J Biol Chem 282:2808-20 (2007)
DOI:10.1074/jbc.M609979200

Reference

PMID:16863919

Authors

Wang ZY, Yang D, Chen Q, Leifer CA, Segal DM, Su SB, Caspi RR, Howard ZO, Oppenheim JJ

Title

Induction of dendritic cell maturation by pertussis toxin and its B subunit differentially initiate Toll-like receptor 4-dependent signal transduction pathways.

Journal

Exp Hematol 34:1115-24 (2006)
DOI:10.1016/j.exphem.2006.04.025

Reference

PMID:15201703

Authors

Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA

Title

Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation.

Journal

Shock 22:57-62 (2004)
DOI:10.1097/01.shk.0000129759.58490.d6

Reference

PMID:17328678

Authors

Lee MS, Kim YJ

Title

Signaling pathways downstream of pattern-recognition receptors and their cross talk.

Journal

Annu Rev Biochem 76:447-80 (2007)
DOI:10.1146/annurev.biochem.76.060605.122847

Reference

PMID:20404851