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2 Introduction

Besides covalently linked protein adhesins, also anchorless cell wall proteins (ACW pro-

teins) mediating adhesion to extracellular matrix components have been identiﬁed. These

proteins lack a signal peptide as well as a common sorting signal like LPXTG and are

secreted by a so far unknown mechanism. Upon secretion they are suggested to be re-

associated to the bacterial cell surface (Chhatwal, 2002). One member of this new group

of adhesins is staphylococcal enolase, which apart from its function as glycolytic enzyme

mediates binding to laminin and thereby might contribute to tissue invasion and blood dis-

semination (Carneiro et al., 2004).

Apart from adhesion, strategies for evasion from the host immune system are crucial

to further promote effective colonisation. Protein A, a covalently linked surface protein

harbouring the LPXTG motive, mediates immune evasion by binding to the FC portion

of immunoglobulin G, thereby hampering efﬁcient opsonisation and subsequent elimina-

tion by professional phagocytes (Foster, 2005). Additional components interfering with the

immune system are staphylokinase, the capsular polysaccharides and so called super-

antigens. By binding to the T-cell receptor and the MHC class II molecule on antigen-

presenting cells, superantigens trigger a T-cell activation that results in the release of pro-

inﬂammatory cytokines (Llewelyn and Cohen, 2002). The excessive uncoordinated release

of pro-inﬂammatory cytokines, in particular TNF α, is thought to be responsible for many of

the clinical features of toxic shock syndrome (Miethke et al., 1992). In addition, S. aureus

avoids the detrimental effects of oxygen free radicals that are formed during the respiratory

burst in professional phagocytes by several mechanisms, including the yellow carotenoid

pigment as scavenger or expression of two superoxide dismutases, which remove superox-

ide radicals (Foster, 2005).

Secreted proteins like the pore-forming α-toxin, hemolysins and other cytolytic toxins (e.g.

leukocydins, Panton-Valentine-leukocydin) lead to the destruction of host cells (Tomita and

Kamio, 1997). Besides this, other toxins cause food poisoning (enterotoxins A-O), the toxic

shock syndrome (TSST-1) or the staphylococcal scalded skin syndrome, which is triggered

by the exfoliative toxins A and B (Ladhani et al., 1999).

Another important feature for the pathogenesis of staphylococcal infections is for exam-

ple the availability of iron in the iron-limited host environment. To this end S. aureus evolved

strategies to sequester iron by synthesis of high afﬁnity iron chelators, siderophores, and

corresponding membrane associated ABC-transporter systems or covalently linked surface

proteins (iron-regulated surface determinant; Isd A, B, C, and H) for the sequestration of

heme complexed iron (Maresso and Schneewind, 2006). The importance of iron home-

ostasis was conﬁrmed by the reduced virulence of a S. aureus mutant lacking the ferric

uptake regulator (fur) in a murine skin abscess model of infection (Horsburgh et al., 2001a).

In fact, S. aureus infections always depend on multiple virulence factors and the high re-

dundancy in the function of virulence factors is supported by several in vivo studies using

mutants lacking for example MSCRAMMs, but not preventing colonisation (Darouiche et al.,

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Crosley CRSH268MW2 Bedienungsanleitung Seite 9