KEGG PATHWAY: ko05150

PATHWAY: ko05150

Entry

ko05150                     Pathway

Name

Staphylococcus aureus infection

Description

Staphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the effectiveness of the immune system: secreting immune modulating proteins that inhibit complement activation and neutrophil chemotaxis or lysis, modulating the sensitivity to cationic antimicrobial peptides (such as defensin) by increasing the positive net charge of its cytoplasmic membrane, and expression of superantigens that prevent development of a normal immune response or cause an emetic response when ingested.

Class

Human Diseases; Infectious disease: bacterial

Pathway map

ko05150

Staphylococcus aureus infection

Disease

H00330

Methicillin-resistant Staphylococcal aureus (MRSA) infection

H00331

Vancomycin-resistant Staphylococcal aureus (VRSA) infection

H01409

Methicillin-sensitive Staphylococcus aureus (MSSA) infection

Orthology

K01315

PLG; plasminogen [EC:3.4.21.7]

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]

K01333

CFI; complement factor I [EC:3.4.21.45]

K01334

CFD; complement factor D [EC:3.4.21.46]

K01335

CFB; complement factor B [EC:3.4.21.47]

K01401

aur; aureolysin [EC:3.4.24.29]

K03367

dltA; D-alanine--poly(phosphoribitol) ligase subunit 1 [EC:6.1.1.13]

K03739

dltB; membrane protein involved in D-alanine export

K03740

dltD; D-alanine transfer protein

K03905

FGG; fibrinogen gamma chain

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

K03991

MBL; mannose-binding lectin

K03992

MASP1; mannan-binding lectin serine protease 1 [EC:3.4.21.-]

K03993

MASP2; mannan-binding lectin serine protease 2 [EC:3.4.21.104]

K03994

C5; complement component 5

K04004

CFH, HF1; complement factor H

K04009

C3AR1; C3a anaphylatoxin chemotactic receptor

K04010

C5AR1, CD88; C5a anaphylatoxin chemotactic receptor 1

K04172

FPR1; formyl peptide receptor 1

K04173

FPRL; formyl peptide receptor-like

K04279

PTAFR; platelet-activating factor receptor

K05230

DEFA; defensin, alpha

K05443

IL10, CSIF; interleukin 10

K05718

ITGAL, CD11a; integrin alpha L

K06461

ITGAM, CD11b; integrin alpha M

K06463

FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III

K06464

ITGB2, CD18; integrin beta 2

K06472

FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a

K06490

ICAM1, CD54; intercellular adhesion molecule 1

K06496

SELP, CD62P; selectin, platelet

K06498

FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I

K06513

FCAR, CD89; CD89 antigen

K06544

SELPLG, CD162; selectin P ligand

K06752

MHC2; MHC class II antigen

K06856

IGH; immunoglobulin heavy chain

K07596

DSG1; desmoglein 1

K07604

KRT1; type I keratin, acidic

K10784

TRAV; T cell receptor alpha chain V region

K10785

TRBV; T-cell receptor beta chain V region

K11038

hlg, luk; leukocidin/hemolysin toxin family protein

K11040

se; staphylococcal enterotoxin

K11041

eta; exfoliative toxin A/B

K11043

tst; toxic shock syndrome toxin-1

K12560

FCGR2B, CD32; low affinity immunoglobulin gamma Fc receptor II-b

K13916

CAMP, LL37; cathelicidin antimicrobial peptide

K14188

dltC; D-alanine--poly(phosphoribitol) ligase subunit 2 [EC:6.1.1.13]

K14192

clfB; clumping factor B

K14193

isdA; iron-regulated surface determinant protein A

K14194

sdrC_D_E; serine-aspartate repeat-containing protein C/D/E

K14195

sasG; surface protein G

K14196

spa; immunoglobulin G-binding protein A

K14197

sbi; immunoglobulin G-binding protein Sbi

K14198

sak; staphylokinase

K14199

scn, scin; staphylococcal complement inhibitor

K14200

fib, efb; fibrinogen-binding protein

K14201

clfA; clumping factor A

K14202

chp, chips; chemotaxis inhibitory protein

K14203

flr, flipr; FPRL1 inhibitory protein

K14204

eap, map; protein Map

K14205

mprF, fmtC; phosphatidylglycerol lysyltransferase [EC:2.3.2.3]

K16824

FCGR2C, CD32; low affinity immunoglobulin gamma Fc receptor II-c

K19079

vraF; cationic antimicrobial peptide transport system ATP-binding protein

K19080

vraG; cationic antimicrobial peptide transport system permease protein

K21100

DEFB4; beta-defensin 4

K23125

DEFB1; beta-defensin 1

K23126

DEFB103; beta-defensin 103

K23586

ssl7, set1; superantigen-like protein 7

K23587

ssl5_11; superantigen-like protein 5/11

Compound

C11596

FMLP

C20898

Lipoteichoic acid

Reference

PMID:20178484

Authors

Foster TJ

Title

Colonization and infection of the human host by staphylococci: adhesion, survival and immune evasion.

Journal

Vet Dermatol 20:456-70 (2009)
DOI:10.1111/j.1365-3164.2009.00825.x

Reference

PMID:16322743

Authors

Foster TJ

Title

Immune evasion by staphylococci.

Journal

Nat Rev Microbiol 3:948-58 (2005)
DOI:10.1038/nrmicro1289

Reference

PMID:20062962

Authors

Laarman A, Milder F, van Strijp J, Rooijakkers S

Title

Complement inhibition by gram-positive pathogens: molecular mechanisms and therapeutic implications.

Journal

J Mol Med 88:115-20 (2010)
DOI:10.1007/s00109-009-0572-y

Reference

PMID:16242332

Authors

Rooijakkers SH, van Kessel KP, van Strijp JA

Title

Staphylococcal innate immune evasion.

Journal

Trends Microbiol 13:596-601 (2005)
DOI:10.1016/j.tim.2005.10.002

Reference

PMID:16679003

Authors

Iwatsuki K, Yamasaki O, Morizane S, Oono T

Title

Staphylococcal cutaneous infections: invasion, evasion and aggression.

Journal

J Dermatol Sci 42:203-14 (2006)
DOI:10.1016/j.jdermsci.2006.03.011

Reference

PMID:11361034

Authors

Torres BA, Kominsky S, Perrin GQ, Hobeika AC, Johnson HM

Title

Superantigens: the good, the bad, and the ugly.

Journal

Exp Biol Med (Maywood) 226:164-76 (2001)
DOI:10.1177/153537020122600303

Reference

PMID:18061675

Authors

Atkins KL, Burman JD, Chamberlain ES, Cooper JE, Poutrel B, Bagby S, Jenkins AT, Feil EJ, van den Elsen JM

Title

S. aureus IgG-binding proteins SpA and Sbi: host specificity and mechanisms of immune complex formation.

Journal

Mol Immunol 45:1600-11 (2008)
DOI:10.1016/j.molimm.2007.10.021

Reference

PMID:16724100

Authors

Silverman GJ, Goodyear CS

Title

Confounding B-cell defences: lessons from a staphylococcal superantigen.

Journal

Nat Rev Immunol 6:465-75 (2006)
DOI:10.1038/nri1853

Reference

PMID:15273292

Authors

Goodyear CS, Silverman GJ

Title

Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes.

Journal

Proc Natl Acad Sci U S A 101:11392-7 (2004)
DOI:10.1073/pnas.0404382101

Reference

PMID:19112495

Authors

Haupt K, Reuter M, van den Elsen J, Burman J, Halbich S, Richter J, Skerka C, Zipfel PF

Title

The Staphylococcus aureus protein Sbi acts as a complement inhibitor and forms a tripartite complex with host complement Factor H and C3b.

Journal

PLoS Pathog 4:e1000250 (2008)
DOI:10.1371/journal.ppat.1000250

Reference

PMID:16111912

Authors

Bokarewa MI, Jin T, Tarkowski A

Title

Staphylococcus aureus: Staphylokinase.

Journal

Int J Biochem Cell Biol 38:504-9 (2006)
DOI:10.1016/j.biocel.2005.07.005

Reference

PMID:16086019

Authors

Rooijakkers SH, Ruyken M, Roos A, Daha MR, Presanis JS, Sim RB, van Wamel WJ, van Kessel KP, van Strijp JA

Title

Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases.

Journal

Nat Immunol 6:920-7 (2005)
DOI:10.1038/ni1235

Reference

PMID:19503103

Authors

Rooijakkers SH, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, Ricklin D, Lambris JD, Janssen BJ, van Strijp JA, Gros P

Title

Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor.

Journal

Nat Immunol 10:721-7 (2009)
DOI:10.1038/ni.1756

Reference

PMID:17893203

Authors

Jongerius I, Kohl J, Pandey MK, Ruyken M, van Kessel KP, van Strijp JA, Rooijakkers SH

Title

Staphylococcal complement evasion by various convertase-blocking molecules.

Journal

J Exp Med 204:2461-71 (2007)
DOI:10.1084/jem.20070818

Reference

PMID:18544012

Authors

Hair PS, Ward MD, Semmes OJ, Foster TJ, Cunnion KM

Title

Staphylococcus aureus clumping factor A binds to complement regulator factor I and increases factor I cleavage of C3b.

Journal

J Infect Dis 198:125-33 (2008)
DOI:10.1086/588825

Reference

PMID:16640587

Authors

Higgins J, Loughman A, van Kessel KP, van Strijp JA, Foster TJ

Title

Clumping factor A of Staphylococcus aureus inhibits phagocytosis by human polymorphonuclear leucocytes.

Journal

FEMS Microbiol Lett 258:290-6 (2006)
DOI:10.1111/j.1574-6968.2006.00229.x

Reference

PMID:20133685

Authors

Laursen NS, Gordon N, Hermans S, Lorenz N, Jackson N, Wines B, Spillner E, Christensen JB, Jensen M, Fredslund F, Bjerre M, Sottrup-Jensen L, Fraser JD, Andersen GR

Title

Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus.

Journal

Proc Natl Acad Sci U S A 107:3681-6 (2010)
DOI:10.1073/pnas.0910565107

Reference

PMID:17848512

Authors

Ramsland PA, Willoughby N, Trist HM, Farrugia W, Hogarth PM, Fraser JD, Wines BD

Title

Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1.

Journal

Proc Natl Acad Sci U S A 104:15051-6 (2007)
DOI:10.1073/pnas.0706028104

Reference

PMID:14993252

Authors

de Haas CJ, Veldkamp KE, Peschel A, Weerkamp F, Van Wamel WJ, Heezius EC, Poppelier MJ, Van Kessel KP, van Strijp JA

Title

Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent.

Journal

J Exp Med 199:687-95 (2004)
DOI:10.1084/jem.20031636

Reference

PMID:17114475

Authors

Prat C, Bestebroer J, de Haas CJ, van Strijp JA, van Kessel KP

Title

A new staphylococcal anti-inflammatory protein that antagonizes the formyl peptide receptor-like 1.

Journal

J Immunol 177:8017-26 (2006)
DOI:10.4049/jimmunol.177.11.8017

Reference

PMID:17132726

Authors

Bestebroer J, Poppelier MJ, Ulfman LH, Lenting PJ, Denis CV, van Kessel KP, van Strijp JA, de Haas CJ

Title

Staphylococcal superantigen-like 5 binds PSGL-1 and inhibits P-selectin-mediated neutrophil rolling.

Journal

Blood 109:2936-43 (2007)
DOI:10.1182/blood-2006-06-015461

Reference

PMID:18045383

Authors

Chung MC, Wines BD, Baker H, Langley RJ, Baker EN, Fraser JD

Title

The crystal structure of staphylococcal superantigen-like protein 11 in complex with sialyl Lewis X reveals the mechanism for cell binding and immune inhibition.

Journal

Mol Microbiol 66:1342-55 (2007)
DOI:10.1111/j.1365-2958.2007.05989.x

Reference

PMID:12091905

Authors

Chavakis T, Hussain M, Kanse SM, Peters G, Bretzel RG, Flock JI, Herrmann M, Preissner KT

Title

Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes.

Journal

Nat Med 8:687-93 (2002)
DOI:10.1038/nm728

Reference

PMID:17517597

Authors

Li M, Lai Y, Villaruz AE, Cha DJ, Sturdevant DE, Otto M

Title

Gram-positive three-component antimicrobial peptide-sensing system.

Journal

Proc Natl Acad Sci U S A 104:9469-74 (2007)
DOI:10.1073/pnas.0702159104

Reference

PMID:15561843

Authors

Sieprawska-Lupa M, Mydel P, Krawczyk K, Wojcik K, Puklo M, Lupa B, Suder P, Silberring J, Reed M, Pohl J, Shafer W, McAleese F, Foster T, Travis J, Potempa J

Title

Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases.

Journal

Antimicrob Agents Chemother 48:4673-9 (2004)
DOI:10.1128/AAC.48.12.4673-4679.2004

Reference

PMID:18837785

Authors

Fraser JD, Proft T

Title

The bacterial superantigen and superantigen-like proteins.

Journal

Immunol Rev 225:226-43 (2008)
DOI:10.1111/j.1600-065X.2008.00681.x