genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
triggered host reaction does not help to fight the causative pathogen, because the T cell
activation is antigen-independent and therefore unspecific to the pathogen. This, together with
induction of immunosuppression, might be one of the advantages which superantigens grant the
bacteria, although the question why bacteria harbor superantigens has not been completely
clarified yet (Herman et al. 1991).
Twenty superantigens of S. aureus have been described so far: toxic shock syndrome toxin-1
(TSST-1), staphylococcal enterotoxins (SE A-E, G-J), and staphylococcal enterotoxin-like toxins (SEL
K-R, U, U2, V). They cause diseases like toxic-shock syndrome and are linked to atopic dermatitis
disease mechanism and allergic rhinitis (Fraser/Proft 2008). Mobile genetic elements of S. aureus
encode the superantigens (Novick RP 2003).
Further immunomodulation is achieved by extracellular adherence protein (Eap), which is also
called MHC class II analogous protein (Map). This protein has similarity to MHC class II molecules
(Jönsson et al. 1995) and influences T cell response during infection in favor of the infecting
S. aureus (Lee et al. 2002). This inhibitory effect on T cells is dose-dependent and occurs only at
high concentrations of Eap, while Eap stimulates T cell proliferation when present in low
concentrations (Haggar et al. 2005).
Virulence of S. aureus is promoted by the ability to attach to the host’s tissue, i. e. to the
host’s extracellular matrix or the host’s cells, by its own surface components. Microbial surface
components recognizing adhesive matrix molecules (MSCRAMMs) mediate the attachment,
which can be regarded as the first initializing step for the establishment of infection
(Gordon RJ/Lowy 2008). Molecules with similar function, but secreted in contrary to the
microbial surface bound MSCRAMMs, are called secretable expanded repertoire adhesive
molecules (SERAMs).
Fibronectin binding proteins A and B (encoded by fnbA and fnbB) have binding properties for
fibronectin, a high molecular weight protein of the host’s extracellular matrix (ECM). S. aureus
also possesses adhesins binding to other ECM components like collagen (collagen binding protein
Cna), elastin (elastin-binding protein EbpS). Clumping factor A and B (encoded by clfA and clfB)
are fibrinogen binding proteins. This property results on the one hand in adhesin function of
clumping factor (Clf). But as Clf can not only bind to the blood coagulation precursor fibrinogen,
but also activate fibrinogen to form fibrin, Clf has on the other hand agglutination properties.
Structurally similar proteins to Clf exist. These are serine-aspartate (SD) repeat proteins, which
are encoded by the genes sdrC, sdrD and sdrE, but their function is still unknown (Foster/Höök
1998).
A MSCRAMM-function of protein A is hypothesized from its ability to bind von-Willebrandfactor
(vWF) in the environment of damaged epithelium where vWF originally enables the
adhesion of platelets (Hartleib et al. 2000). Interestingly, a novel vWF binding protein (vWBP,
encoded by vwb) of S. aureus has been discovered more recently (Bjerketorp et al. 2002).
Fibronectin-binding protein (FnBP), clumping factor A (ClfA), protein A (Spa), and collagen
binding protein (Cna) belong to the same group of MSCRAMMs. They contain a LPXTG motif
which is cleaved during protein secretion through the cellular membrane with sequential
anchoring of the remaining protein via the now accessible carboxylgroup of threonin (T) to the
cell wall peptidoglycan (Foster/Höök 1998). Further MSCRAMMs in S. aureus are laminin-,
vitronectin-, thrombospondin- and bone sialoprotein-binding proteins (Patti et al. 1994).
MSCRAMMs do not only mediate the adhesion to the host’s extracellular matrix, but they are
also involved in invasion into the host cells. Fibronectin-binding proteins attach the bacterial cell
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