KEGG   PATHWAY: ko05133
ko05133                     Pathway                                
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.
Human Diseases; Infectious disease: bacterial
Pathway map
ko05133  Pertussis

M00574  Pertussis pathogenicity signature, pertussis toxin [PATH:ko05133]
M00575  Pertussis pathogenicity signature, T1SS [PATH:ko05133]
H00319  Pertussis
K12681  pertactin
K07345  major type 1 subunit fimbrin (pilin)
K07347  outer membrane usher protein
K06484  integrin alpha 5
K05719  integrin beta 1
K07326  hemolysin activation/secretion protein
K12688  autotransporter serine protease [EC:3.4.21.-]
K15125  filamentous hemagglutinin
K06461  integrin alpha M
K06464  integrin beta 2
K11004  ATP-binding cassette, subfamily B, bacterial HlyB/CyaB
K11003  membrane fusion protein, hemolysin D
K12340  outer membrane protein
K07389  cytolysin-activating lysine-acyltransferase [EC:2.3.1.-]
K22944  bifunctional hemolysin/adenylate cyclase [EC:]
K02183  calmodulin
K04513  Ras homolog gene family, member A
K05765  cofilin
K02187  caspase 3 [EC:]
K04397  caspase 7 [EC:]
K01370  caspase 1 [EC:]
K12799  apoptosis-associated speck-like protein containing a CARD
K12800  NACHT, LRR and PYD domains-containing protein 3
K04519  interleukin 1 beta
K12683  serum resistance protein
K03986  complement C1q subcomponent subunit A
K03987  complement C1q subcomponent subunit B
K03988  complement C1q subcomponent subunit C
K01330  complement component 1, r subcomponent [EC:]
K01331  complement component 1, s subcomponent [EC:]
K01332  complement component 2 [EC:]
K03989  complement component 4
K03990  complement component 3
K03994  complement component 5
K04001  C1 inhibitor
K04002  complement component 4 binding protein alpha
K04003  complement component 4 binding protein beta
K12973  lipid IVA palmitoyltransferase [EC:]
K05400  lymphocyte antigen 96
K10160  toll-like receptor 4
K04391  monocyte differentiation antigen CD14
K05403  toll-interleukin 1 receptor (TIR) domain-containing adaptor protein
K04729  myeloid differentiation primary response protein MyD88
K04733  interleukin-1 receptor-associated kinase 4 [EC:]
K04730  interleukin-1 receptor-associated kinase 1 [EC:]
K03175  TNF receptor-associated factor 6 [EC:]
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K05409  TRIF-related adaptor molecule
K05842  toll-like receptor adapter molecule 1
K05411  interferon regulatory factor 3
K04441  p38 MAP kinase [EC:]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K04379  proto-oncogene protein c-fos
K04448  transcription factor AP-1
K05405  interleukin 6
K05406  interleukin 12A
K05425  interleukin 12B
K05426  interleukin 23 subunit alpha
K03156  tumor necrosis factor superfamily, member 2
K05443  interleukin 10
K09444  interferon regulatory factor 1
K10155  interferon regulatory factor 8
K10067  pulmonary surfactant-associated protein A
K11023  pertussis toxin subunit 1 [EC:2.4.2.-]
K11024  pertussis toxin subunit 2
K11025  pertussis toxin subunit 3
K11026  pertussis toxin subunit 4
K11027  pertussis toxin subunit 5
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K10030  interleukin 8
K05506  C-X-C motif chemokine 5/6
K08727  nucleotide-binding oligomerization domain-containing protein 1
K04383  interleukin 1 alpha
K13241  nitric-oxide synthase, inducible [EC:]
K15126  type III secretion system cytotoxic effector protein
K07679  two-component system, NarL family, sensor histidine kinase EvgS [EC:]
K07690  two-component system, NarL family, response regulator EvgA
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
de Gouw D, Diavatopoulos DA, Bootsma HJ, Hermans PW, Mooi FR
Pertussis: a matter of immune modulation.
FEMS Microbiol Rev 35:441-74 (2011)
Carbonetti NH
Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools.
Future Microbiol 5:455-69 (2010)
van den Berg BM, van Furth R, Hazenbos WL
Activation of complement receptor 3 on human monocytes by cross-linking of very-late antigen-5 is mediated via protein tyrosine kinases.
Immunology 98:197-202 (1999)
Mazar J, Cotter PA
Topology and maturation of filamentous haemagglutinin suggest a new model for two-partner secretion.
Mol Microbiol 62:641-54 (2006)
Hewlett EL, Donato GM, Gray MC
Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: more than just making cyclic AMP!
Mol Microbiol 59:447-59 (2006)
Dunne A, Ross PJ, Pospisilova E, Masin J, Meaney A, Sutton CE, Iwakura Y, Tschopp J, Sebo P, Mills KH
Inflammasome activation by adenylate cyclase toxin directs Th17 responses and protection against Bordetella pertussis.
J Immunol 185:1711-9 (2010)
Hickey FB, Brereton CF, Mills KH
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.
J Leukoc Biol 84:234-43 (2008)
Spensieri F, Fedele G, Fazio C, Nasso M, Stefanelli P, Mastrantonio P, Ausiello CM
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.
Infect Immun 74:2831-8 (2006)
Fiser R, Masin J, Basler M, Krusek J, Spulakova V, Konopasek I, Sebo P
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.
J Biol Chem 282:2808-20 (2007)
Wang ZY, Yang D, Chen Q, Leifer CA, Segal DM, Su SB, Caspi RR, Howard ZO, Oppenheim JJ
Induction of dendritic cell maturation by pertussis toxin and its B subunit differentially initiate Toll-like receptor 4-dependent signal transduction pathways.
Exp Hematol 34:1115-24 (2006)
Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA
Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation.
Shock 22:57-62 (2004)
Lee MS, Kim YJ
Signaling pathways downstream of pattern-recognition receptors and their cross talk.
Annu Rev Biochem 76:447-80 (2007)
Kawai T, Akira S
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
Nat Immunol 11:373-84 (2010)
Ferlito M, Romanenko OG, Guyton K, Ashton S, Squadrito F, Halushka PV, Cook JA
Implication of Galpha i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator production.
J Endotoxin Res 8:427-35 (2002)
Han HJ, Kuwae A, Abe A, Arakawa Y, Kamachi K
Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis.
PLoS One 6:e17797 (2011)
Beier D, Gross R
Regulation of bacterial virulence by two-component systems.
Curr Opin Microbiol 9:143-52 (2006)
Cotter PA, Jones AM
Phosphorelay control of virulence gene expression in Bordetella.
Trends Microbiol 11:367-73 (2003)
ko02020  Two-component system
ko03070  Bacterial secretion system
ko04010  MAPK signaling pathway
ko04210  Apoptosis
ko04610  Complement and coagulation cascades
ko04620  Toll-like receptor signaling pathway

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