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Chapter 31 : The Pathogenicity Island

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The Pathogenicity Island, Page 1 of 2

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Abstract:

This chapter focuses on the functions that are encoded by a 40-kb chromosomal region with the features of a pathogenicity island (PAI). The PAI was originally named cytotoxin-associated gene () since it was thought to be associated with expression of the vacuolating toxin (VacA). The module also forms the core of the left and right ends of an insertion sequence common in , the IS605 element. One of the most exciting research areas in microbial pathogenesis over the past decade has been the exploration of type III secretion systems. The type IV secretion system can translocate virulence proteins into the host cells. The resulting protrusions on the cell surface (pedestals) somehow resemble the cup-like structures induced by , although they are clearly different structures. Recent observations characterized the involvement of the PAI in phagocytosis of . Mononuclear phagocytes were shown to engulf within approximately 4 minutes, but the internalized bacteria were not killed if type I strains were used for the infection. Instead, induced homotypic phagosome fusions leading to the formation of large vacuoles. The function of the (PAI) in -associated disease has been the subject of controversy ever since its discovery in 1993. Clinical studies with different outcomes have been performed to test whether the presence of the PAI is connected with peptic ulcer disease or gastric cancer. Future approaches have to consider that the presence of the gene alone is not equal to virulence.

Citation: Stein M, Rappouli R, Covacci A. 2001. The Pathogenicity Island, p 345-353. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch31

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Bacterial Proteins
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Type IV Secretion Systems
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Type III Secretion System
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Bacterial Secretion Systems
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Figures

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Figure 1

Genetic organization of the pathogenicity island. The open reading frames within the 40-kb PAI are depicted as arrows with the gene designations (single letters) below and names of homologs above. The whole genome gene designations are given as a three-digit number. Below, three alternative arrangements of the PAI in three additional strains are shown, is an insertion sequence; tnpA, transposon A; tnpB, transposon B.

Citation: Stein M, Rappouli R, Covacci A. 2001. The Pathogenicity Island, p 345-353. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch31
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Image of Figure 2
Figure 2

Activation of CagA and intracellular actin condensation. Translocation is mediated by the TFSS (a); activation is dependent by a membrane-associated host kinase (b, c) that phosphorylate CagA at multiple sites; small GTP-binding proteins may be involved in recruitment of the N-WASP and Arp 2/3 complex for cortical actin polymerization (d).

Citation: Stein M, Rappouli R, Covacci A. 2001. The Pathogenicity Island, p 345-353. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch31
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Figure 3

Cellular responses to CagA activation. Isolated cells forming the structure of an epithelium are represented during contacts with type I strains of (defined as positive for expression, translocation, and activation of CagA). Two predominant classes of signals are indicated: signals for inflammation and signals for autocrine stimulation and cell cycle control.

Citation: Stein M, Rappouli R, Covacci A. 2001. The Pathogenicity Island, p 345-353. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch31
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Figure 4

Mutations affecting CagA activation, (a) Mutations in CagA expression and structure, (b) mutations in the component of the type IV secretion system, and (c) mutations for absence of phosphorylated CagA or for absence or unresponsiveness of intracellular targets.

Citation: Stein M, Rappouli R, Covacci A. 2001. The Pathogenicity Island, p 345-353. In Mobley H, Mendz G, Hazell S (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555818005.ch31
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