Chapter 3 : Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease

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This chapter presents a review of the invasins and pathways used by to reach the intracellular state, and discusses the relationship between intracellular invasion and human disease. Intracellular invasion depends on at least two classes of surface proteins, the M proteins and fibronectin (Fn)-binding proteins. The function of these proteins in the context of intracellular invasion is described in the chapter. The best and most direct evidence that intracellular bacteria are an important source for dissemination of streptococci and the cause of recurrent tonsillitis is based on microscopic studies of surgically excised tonsils. Invasins are a subclass of bacterial adhesin molecules required for ingestion by host cells. Typically, invasions are proteins expressed on the surfaces of bacterial cells that directly or indirectly recognize specific host cell receptors. The internalization by a zipper mechanism is mediated by interactions between surface invasins, ligands, and host cell receptors. Studies of streptococcal-induced signal-transduction pathways have focused on two major invasins and Fn-binding proteins, SfbI/PrtF1 and M1 protein. The spectrum of target host cells, invasion efficiency, and requirement for serum agonists is determined by the extracellular matrix-binding proteins displayed on the bacterial surface. No single invasin or surface protein accounts for high-efficiency invasion of epithelial cells by all strains of streptococci. These findings suggest that intracellular invasion may be triggered by different agonists in different tissues or at different stages of infection.

Citation: Wang B, Cue D, Cleary P. 2006. Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease, p 29-36. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch3

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Bacterial Proteins
Outer Membrane Proteins
Streptococcus pyogenes
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Image of FIGURE 1

Scanning electron micrographs showing different stages of streptococcal-HeLa cell interactions. (A) A high density of microvilli surrounding and in contact with adherent streptococci. (B) A common morphological change that microvilli undergo. The cup-like structure appears to gradually engulf the bacteria and ultimately pulls them into a vacuole. (C) A streptococcal chain has been partially ingested by a mechanism that morphologically resembles a receptor-ligand interaction. It is not known whether microvilli are involved in the latter or whether streptococci are ingested by two different kinds of cytoskeletal rearrangements.

Citation: Wang B, Cue D, Cleary P. 2006. Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease, p 29-36. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch3
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Image of FIGURE 2

This cartoon depicts the various agonist and cellular receptors that streptococci commandeer to promote their own phagocytosis by epithelial cells. Both the M protein and high-affinity Fn proteins SfbI/PrtF1 are known invasins that depend on Fn forming a bridge between the bacterial surface and integrin receptors α5β1 or αVβ3. Although less studied, Ln can also serve as an agonist for ingestion of streptococci by bridging them to α3β1 integrins. For some strains Fn-mediated invasion of epithelial cells also requires interaction between M protein and the complement regulatory protein CD46.

Citation: Wang B, Cue D, Cleary P. 2006. Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease, p 29-36. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch3
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Image of FIGURE 3

Postulated and confirmed components of streptococcal-induced focal adhesion complexes and signaling molecules required for formation of those complexes and subsequent cytoskeletal changes that lead to ingestion of streptococci by epithelial cells. Fn bound to surface M1 or SfbI/PrtF1 proteins associates with integrins to cause integrin clustering, leading to ILK activation in a PI3K-dependent manner. For some strains contact between M protein and CD46 is also required for high-level invasion. The function of CD46 in this process, however, is unknown. Following recruitment of paxillin, FAK, and other focal adhesion proteins, autophosphorylation of FAK creates a docking site for Src kinases to phosphorylate recruited paxillin and additional phosphorylation sites of FAK. Alternatively, Rac and Cdc42 are activated by ILK through an intermediate to participate in formation of focal adhesion complexes, which provide an anchor for actin polymerization and cytoskeleton rearrangement, and ultimately results in uptake of .

Citation: Wang B, Cue D, Cleary P. 2006. Intracellular Invasion by : Invasins, Host Receptors, and Relevance to Human Disease, p 29-36. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch3
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