Adherence of Staphylococcus aureus to the host tissue is an important step in the initiation of pathogenesis. At least 10 adhesins produced by S. aureus have been described and it is becoming clear that the expression of these adhesins and their interactions with eukaryotic cells involve complex processes. Some of these, such as the fibronectin-binding proteins (FnBPs) and Clumping Factor A, are well characterized. However, in the last 10 years a number of novel S. aureus adhesins have been described. Functional analyses of these proteins, one of which is Eap (extracellular adherence protein, also known as Map and p70), are revealing important information on the pathogenesis of staphylococcal disease. More than 10 years after the first report of Eap, we are beginning to understand that this protein, which has a broad spectrum of functions, may be a critical factor in the pathogenesis of S. aureus. This review will focus on the interactions of Eap with eukaryotic cells, plasma proteins and the extracellular matrix as well as on the recently recognized role of Eap as an important mediator in the immune response to staphylococcal infection.
BodénM. K.,
FlockJ. I.1992; Evidence for three different fibrinogen-binding proteins with unique properties from Staphylococcus aureus strain Newman. Microb Pathog 12:289–298
CabanasC.,
HoggN.1993; Ligand intercellular adhesion molecule 1 has a necessary role in activation of integrin lymphocyte function-associated molecule 1. Proc Natl Acad Sci U S A 90:5838–5842
ChavakisT.,
HussainM.,
KanseS. M.,
PetersG.,
BretzelR. G.,
FlockJ. I.,
HerrmannM.,
PreissnerK. T.2002; Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nat Med 8:687–693
DunmanP. M.,
MurphyE.,
HaneyS.7 other authors2001; Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J Bacteriol 183:7341–7353
DziewanowskaK.,
PattiJ. M.,
DeobaldC. F.,
BaylesK. W.,
TrumbleW. R.,
BohachG. A.1999; Fibronectin binding protein and host cell tyrosine kinase are required for internalization of Staphylococcus aureus by epithelial cells. Infect Immun 67:4673–4678
FlockM.,
FlockJ. I.2001; Rebinding of extracellular adherence protein Eap to Staphylococcus aureus can occur through a surface-bound neutral phosphatase. J Bacteriol 183:3999–4003
HussainM.,
BeckerK.,
von EiffC.,
PetersG.,
HerrmannM.2001; Analogs of Eap protein are conserved and prevalent in clinical Staphylococcus aureus isolates. Clin Diagn Lab Immunol 8:1271–1276
JahreisA.,
YousifY.,
RumpJ. A.,
DragerR.,
VogtA.,
PeterH. H.,
SchlesierM.1995; Two novel cationic staphylococcal proteins induce IL-2 secretion, proliferation and immunoglobulin synthesis in peripheral blood mononuclear cells (PBMC) of both healthy controls and patients with common variable immunodeficiency (CVID. Clin Exp Immunol 100:406–411
JahreisA.,
BeckheinrichP.,
HausteinU. F.2000; Effects of two novel cationic staphylococcal proteins (NP-tase and p70) and enterotoxin B on IgE synthesis and interleukin-4 and interferon-gamma production in patients with atopic dermatitis. Br J Dermatol 142:680–687
JonssonK.,
McDevittD.,
McGavinM. H.,
PattiJ. M.,
HookM.1995; Staphylococcus aureus expresses a major histocompatibility complex class II analog. J Biol Chem 270:21457–21460
KreikemeyerB.,
McDevittD.,
PodbielskiA.2002; The role of the map protein in Staphylococcus aureus matrix protein and eukaryotic cell adherence. Int J Med Microbiol 292:283–295
LeeL. Y.,
MiyamotoY. J.,
McIntyreB. W.,
HookM.,
McCreaK. W.,
McDevittD.,
BrownE. L.2002; The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses. J Clin Invest 110:1461–1471
MazmanianS. K.,
LiuG.,
Ton-ThatH.,
SchneewindO.1999; Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall. Science 285:760–763
McGavinM. H.,
Krajewska-PietrasikD.,
RydenC.,
HookM.1993; Identification of a Staphylococcus aureus extracellular matrix-binding protein with broad specificity. Infect Immun 61:2479–2485
PalmaM.,
HaggarA.,
FlockJ. I.1999; Adherence of Staphylococcus aureus is enhanced by an endogenous secreted protein with broad binding activity. J Bacteriol 181:2840–2845
RheeJ.-S.,
SantosoS.,
HerrmannM.7 other authors2003; New aspects of integrin-mediated leukocyte adhesion in inflammation: regulation by haemostatic factors and bacterial products. Curr Mol Med 3:387–392
SantinA. D.,
HermonatP. L.,
RavaggiA.,
Chiriva-InternatiM.,
CannonM. J.,
HiserodtJ. C.,
PercorelliS.,
ParhamG. P.1999; Expression of surface antigens during the differentiation of human dendritic cells vs . macrophages from blood monocytes in vitro . Immunobiology 200:187–204
SinhaB.,
FrançoisP. P.,
NuesseO.7 other authors1999; Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin α5β1
. Cell Microbiol 1:101–117
VerdrenghM.,
SpringerT. A.,
Gutierrez-RamosJ. C.,
TarkowskiA.1996; Role of intercellular adhesion molecule 1 in pathogenesis of staphylococcal arthritis and in host defense against staphylococcal bacteremia. Infect Immun 64:2804–2807
VuongC.,
KellerD.,
PeschelA.,
OttoM.2002; Binding of the Map protein of Staphylococcus aureus Newman to the cell wall is dependent on the d-alanylation of teichoic acids. In 10th International Symposium on Staphylococci and Staphylococcal Infections p 43 Tsukuba, Japan: ISSSI 102-Abstract 01;
YoshimotoT.,
PaulW. E.1994; CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med 179:1285–1295
YousifY.,
MertzA.,
BatsfordS. R.,
VogtA.1991; Cationic staphylococcal antigens have high affinity for glomerular structures. Possible pathogenic role in glomerulonephritis. Zentbl Bakteriol 21:Suppl168–169