KEGG   PATHWAY: hsa05133Help
Entry
hsa05133                    Pathway                                
Name
Pertussis - Homo sapiens (human)
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 diseases
BRITE hierarchy
Pathway map
Pertussis
hsa05133

All organismsOrtholog table
Module
Pertussis pathogenicity signature 1, pertussis toxin [PATH:hsa05133]
Pertussis pathogenicity signature 2, T1SS [PATH:hsa05133]
Disease
H00319  
Pertussis
Organism
Homo sapiens (human) [GN:hsa]
Gene
3678  
ITGA5; integrin, alpha 5 (fibronectin receptor, alpha polypeptide) [KO:K06484]
3688  
ITGB1; integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) [KO:K05719]
3684  
ITGAM; integrin, alpha M (complement component 3 receptor 3 subunit) [KO:K06461]
3689  
ITGB2; integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) [KO:K06464]
810  
CALML3; calmodulin-like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [KO:K02183]
387  
RHOA; ras homolog family member A [KO:K04513]
1072  
CFL1; cofilin 1 (non-muscle) [KO:K05765]
1073  
CFL2; cofilin 2 (muscle) [KO:K05765]
836  
CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
840  
CASP7; caspase 7, apoptosis-related cysteine peptidase [KO:K04397] [EC:3.4.22.60]
834  
CASP1; caspase 1, apoptosis-related cysteine peptidase [KO:K01370] [EC:3.4.22.36]
29108  
PYCARD; PYD and CARD domain containing [KO:K12799]
114548  
NLRP3; NLR family, pyrin domain containing 3 [KO:K12800]
3553  
IL1B; interleukin 1, beta [KO:K04519]
712  
C1QA; complement component 1, q subcomponent, A chain [KO:K03986]
713  
C1QB; complement component 1, q subcomponent, B chain [KO:K03987]
714  
C1QC; complement component 1, q subcomponent, C chain [KO:K03988]
715  
C1R; complement component 1, r subcomponent [KO:K01330] [EC:3.4.21.41]
716  
C1S; complement component 1, s subcomponent [KO:K01331] [EC:3.4.21.42]
717  
C2; complement component 2 [KO:K01332] [EC:3.4.21.43]
720  
C4A; complement component 4A (Rodgers blood group) [KO:K03989]
721  
C4B; complement component 4B (Chido blood group) [KO:K03989]
718  
C3; complement component 3 [KO:K03990]
727  
C5; complement component 5 [KO:K03994]
710  
SERPING1; serpin peptidase inhibitor, clade G (C1 inhibitor), member 1 [KO:K04001]
722  
C4BPA; complement component 4 binding protein, alpha [KO:K04002]
725  
C4BPB; complement component 4 binding protein, beta [KO:K04003]
23643  
LY96; lymphocyte antigen 96 [KO:K05400]
7099  
TLR4; toll-like receptor 4 [KO:K10160]
929  
CD14; CD14 molecule [KO:K04391]
114609  
TIRAP; toll-interleukin 1 receptor (TIR) domain containing adaptor protein [KO:K05403]
4615  
MYD88; myeloid differentiation primary response 88 [KO:K04729]
51135  
IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3654  
IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
7189  
TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
353376  
TICAM2; toll-like receptor adaptor molecule 2 [KO:K05409]
148022  
TICAM1; toll-like receptor adaptor molecule 1 [KO:K05842]
3661  
IRF3; interferon regulatory factor 3 [KO:K05411]
5600  
MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  
MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  
MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  
MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
3725  
JUN; jun proto-oncogene [KO:K04448]
3569  
IL6; interleukin 6 (interferon, beta 2) [KO:K05405]
3592  
IL12A; interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35) [KO:K05406]
3593  
IL12B; interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) [KO:K05425]
51561  
IL23A; interleukin 23, alpha subunit p19 [KO:K05426]
7124  
TNF; tumor necrosis factor [KO:K03156]
3586  
IL10; interleukin 10 [KO:K05443]
3659  
IRF1; interferon regulatory factor 1 [KO:K09444]
3394  
IRF8; interferon regulatory factor 8 [KO:K10155]
653509  
SFTPA1; surfactant protein A1 [KO:K10067]
729238  
SFTPA2; surfactant protein A2 [KO:K10067]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
3576  
IL8; interleukin 8 [KO:K10030]
6374  
CXCL5; chemokine (C-X-C motif) ligand 5 [KO:K05506]
6372  
CXCL6; chemokine (C-X-C motif) ligand 6 [KO:K05506]
10392  
NOD1; nucleotide-binding oligomerization domain containing 1 [KO:K08727]
3552  
IL1A; interleukin 1, alpha [KO:K04383]
4843  
NOS2; nitric oxide synthase 2, inducible [KO:K13241] [EC:1.14.13.39]
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
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  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)
Reference
  Authors
Kawai T, Akira S
  Title
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
  Journal
Nat Immunol 11:373-84 (2010)
Reference
  Authors
Ferlito M, Romanenko OG, Guyton K, Ashton S, Squadrito F, Halushka PV, Cook JA
  Title
Implication of Galpha i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator production.
  Journal
J Endotoxin Res 8:427-35 (2002)
Reference
  Authors
Han HJ, Kuwae A, Abe A, Arakawa Y, Kamachi K
  Title
Differential expression of type III effector BteA protein due to IS481 insertion  in Bordetella pertussis.
  Journal
PLoS One 6:e17797 (2011)
Reference
  Authors
Beier D, Gross R
  Title
Regulation of bacterial virulence by two-component systems.
  Journal
Curr Opin Microbiol 9:143-52 (2006)
Reference
  Authors
Cotter PA, Jones AM
  Title
Phosphorelay control of virulence gene expression in Bordetella.
  Journal
Trends Microbiol 11:367-73 (2003)
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