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
Disease
H00319  
Pertussis
Organism
Homo sapiens (human) [GN:hsa]
Gene
3678  
ITGA5; integrin subunit alpha 5 [KO:K06484]
3688  
ITGB1; integrin subunit beta 1 [KO:K05719]
3684  
ITGAM; integrin subunit alpha M [KO:K06461]
3689  
ITGB2; integrin subunit beta 2 [KO:K06464]
810  
CALML3; calmodulin like 3 [KO:K02183]
805  
CALM2; calmodulin 2 [KO:K02183]
808  
CALM3; calmodulin 3 [KO:K02183]
801  
CALM1; calmodulin 1 [KO:K02183]
163688  
CALML6; calmodulin like 6 [KO:K02183]
51806  
CALML5; calmodulin like 5 [KO:K02183]
91860  
CALML4; calmodulin like 4 [KO:K02183]
387  
RHOA; ras homolog family member A [KO:K04513]
1072  
CFL1; cofilin 1 [KO:K05765]
1073  
CFL2; cofilin 2 [KO:K05765]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
840  
CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
834  
CASP1; caspase 1 [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 C1q A chain [KO:K03986]
713  
C1QB; complement C1q B chain [KO:K03987]
714  
C1QC; complement C1q C chain [KO:K03988]
715  
C1R; complement C1r [KO:K01330] [EC:3.4.21.41]
716  
C1S; complement C1s [KO:K01331] [EC:3.4.21.42]
717  
C2; complement C2 [KO:K01332] [EC:3.4.21.43]
720  
C4A; complement C4A (Rodgers blood group) [KO:K03989]
721  
C4B; complement C4B (Chido blood group) [KO:K03989]
718  
C3; complement C3 [KO:K03990]
727  
C5; complement C5 [KO:K03994]
710  
SERPING1; serpin family G 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; 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 [KO:K03175] [EC:2.3.2.27]
4790  
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
RELA; RELA proto-oncogene, NF-kB subunit [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; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
3725  
JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
3569  
IL6; interleukin 6 [KO:K05405]
3592  
IL12A; interleukin 12A [KO:K05406]
3593  
IL12B; interleukin 12B [KO:K05425]
51561  
IL23A; interleukin 23 subunit alpha [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; G protein subunit alpha i1 [KO:K04630]
2773  
GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  
GNAI2; G protein subunit alpha i2 [KO:K04630]
3576  
CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
6374  
CXCL5; C-X-C motif chemokine ligand 5 [KO:K05506]
6372  
CXCL6; C-X-C motif chemokine 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 [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)
DOI:10.1111/j.1574-6976.2010.00257.x
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)
DOI:10.2217/fmb.09.133
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)
DOI:10.1046/j.1365-2567.1999.00871.x
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)
DOI:10.1111/j.1365-2958.2006.05392.x
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)
DOI:10.1111/j.1365-2958.2005.04958.x
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)
DOI:10.4049/jimmunol.1000105
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)
DOI:10.1189/jlb.0208113
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)
DOI:10.1128/IAI.74.5.2831-2838.2006
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)
DOI:10.1074/jbc.M609979200
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)
DOI:10.1016/j.exphem.2006.04.025
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)
DOI:10.1146/annurev.biochem.76.060605.122847
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)
DOI:10.1038/ni.1863
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)
DOI:10.1371/journal.pone.0017797
Reference
  Authors
Beier D, Gross R
  Title
Regulation of bacterial virulence by two-component systems.
  Journal
Curr Opin Microbiol 9:143-52 (2006)
DOI:10.1016/j.mib.2006.01.005
Reference
  Authors
Cotter PA, Jones AM
  Title
Phosphorelay control of virulence gene expression in Bordetella.
  Journal
Trends Microbiol 11:367-73 (2003)
DOI:10.1016/S0966-842X(03)00156-2
KO pathway
 

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