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Chapter 10 : , the Pathogenicity Island of , Triggers Host Responses

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Abstract:

was isolated by accidental extended incubation. It is a spiral-shaped, gram-negative, microaerophilic microorganism that colonizes and survives in the hostile environment of the human stomach, in an equilibrium that permanently links the parasite to the host. Strains isolated from patients with peptic ulcer disease (PUD) contain the cagA gene (cytotoxin-associated gene A) and express the immunodominant CagA antigen. CagA and VacA are frequently coexpressed; however, their genes are 300 kb apart and VacA expression does not require the presence of the cagA gene, since null mutants still produce the VacA protein. In most industrialized countries, 70 to 80% of the clinical isolates express CagA. Clinical isolates have been grouped into two broad families, type I and type II, in which type I strains possess the pathogenicity island (PAI). As with the related Cag proteins of , the Icm/Dot proteins act as an exporters for the virulence factor(s) targeted to the intracellular environment to enhance survival and to kill host macrophages. The existence of 30 different proteins all encoded within underscores the functional importance of specialized chaperones in macromolecular export. Recent data suggest that VirB4, VirB7, VirB9, VirBlO, and VirB 11 assemble as a complex and form the core of the transporter. The diffusion of entails the spread of a population's culture. This was influenced by the history of parasitic association of the bacterium with the human species and the migratory expansion.

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10

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Type III Secretion System
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Type IV Secretion Systems
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Type III Secretion System
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Type IV Secretion Systems
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Image of Figure 1
Figure 1

(a) Map of the region, genes marked with letters (A or B, for example) refer to the nomenclature suggested by Censini et al. ( ); numbers refer to the list of open reading frames compiled by Tomb et al. ( ) that is based on the complete genome sequence. Proteins with leader sequences are identified with letters and/or numbers above the arrows, homologs of the and regions of are listed. Squares with triangles represent the 31 direct repeats, (b) i, ii, and iii are recombinational events mediated by an 1S605 insertion that generates the intervening sequence found in strain CCUG 17874.

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10
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Image of Figure 2
Figure 2

Evolution of type I, intermediate, and type II strains, acquisition is indicated by an arrow. The white circle indicates the IS insertion. The type I and type II lineages show little divergence. Intermediate strains branch from type I, and the level of fragmentation is progressively increasing (top to bottom). All intermediate strains are positive for IS. A tentative bar scale is indicated and was obtained by computer simulation calculated on the basis of DNA amelioration rates.

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10
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Figure 3

Model illustrating cycles of contraction and expansion of the population during a chronic infection. Open circles represent bacteria, and solid circles represent bacteria. Loss of the PAI is the most frequent event in vivo, (a) After infection with a type I strain, the acute phase is dominated by bacteria, (b and c) During the remission phase, clones, originated by selective pressure, expanded, (d and e) After remission, another wave of clonal expansion of bacteria starts. This model was originally proposed by J. Hacker to explain chronic urinary infections by 536.

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10
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Image of Figure 4
Figure 4

Evolutionary relationships between members of the type IV secretion apparatuses. Boxes indicate individual gene products, and the order reflects their relative position within the operons. Functions and localization are provided for each member. The shaded areas refer to the minimal set of Vir homologs present within .

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10
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Image of Figure 5
Figure 5

Chain of events following attachment of type I to an epithelial cell in culture, (a) Pedestal induction, (b) Growth of the Pseudopodium and triggering of intracellular reactions, (c) Resulting tyrosine phosphorylation of the 145-kDa protein localized in the membrane fraction, (d) Resulting activation of NF-B and IL-8 secretion.

Citation: Covacci A, Rappuoli R. 1999. , the Pathogenicity Island of , Triggers Host Responses, p 189-202. In Kaper J, Hacker J (ed), Pathogenicity Islands and Other Mobile Virulence Elements. ASM Press, Washington, DC. doi: 10.1128/9781555818173.ch10
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