genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
contains all properties for its own insertion into membranes and therefore needs no assistance
by proteins like chaperones (Menestrina et al. 2001). Other cytolytic toxins of S. aureus are betahemolysin
(hlb), gamma-hemolysin (hlgA, hlgB, hlgC), delta-hemolysin (hld), and the groups of
leukocidins (luk). The Panton-Valentine leukocidin (PVL, lukF-PV and lukS-PV), a long-known and
well-studied bicomponent toxin, depends in its pore-forming activity on two components, which
first form themselves a heterodimer (Kaneko/Kamio 2004). Also the other leukocidins and Hlg are
bicomponent lysins. Hlg can form either the AB toxin or the CB toxin depending on the
association of the subunits to heterodimers.
Fig. I.4: Staphylococcal structural and secreted virulence factors.
A. Overview on surface and secreted proteins. TSST-1 – toxic shock syndrome toxin 1.
B. Cell envelope structure and localization of selected proteins.
C. Domains of cell wall anchored proteins.
From: Gordon/Lowy 2008.
Other important staphylococcal exotoxins are the so-called superantigens (SAg). These
proteins disturb the host’s cellular adaptive immune response. Normally, T cells bind with their
antigenic-peptide specific receptor (T-cell-receptor, TCR) to MHC-molecules, which present
peptides derived from proteins inside or outside the antigen-presenting cell. This forms the socalled
“immunological synapse” between antigen-presenting cell (APC) and T cell. In case of both
specific recognition of the peptide by TCR as well as presence of further pro-stimulatory signals,
the T cell will be activated, start to proliferate and secrete cytokines, and in general pursue their
function in immune response. Superantigens interfere in this interaction. They can bind MHC-IImolecules
on APC (with different preferences for MHC class II alleles) and also the TCR, in detail a
subset of possible recombined TCR molecules characterized by certain Vβ-fragments in the β-
chain (Herman et al. 1991). By this means, they build a bridge linking both receptors
independently of an antigenic peptide and receptor specificity. This cross-linking in the
trimolecular complex TCR/MHC-II/SAg induces a massive T cell proliferation and cytokine
production leading to shock-like syndromes and generalized life-threatening damage. But the
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