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Cited by 508

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin‐8

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Fischer, Wolfgang, Püls, Jürgen, Buhrdorf, Renate, Gebert, Bettina, Odenbreit, Stefan, Haas, Rainer·2001·Molecular Microbiology

Abstract

Helicobacter pylori (Hp) carries a type IV secretion system encoded by the cag pathogenicity island (cag‐PAI), which is used to: (i) translocate the bacterial effector protein CagA into different types of eukaryotic cells; and (ii) induce the synthesis and secretion of chemokines, such as interleukin‐8 (IL‐8). The cag‐PAI in Hp 26695 consists of 27 putative genes, six of which were identified as homologues to the basic type IV secretion system represented by the Agrobacterium tumefaciens virB operon. To define the role and contribution of each of the 27 genes, we applied a precise deletion/insertion mutagenesis procedure to knock out each individual gene without causing polar effects on the expression of downstream genes. Seventeen out of 27 genes were found to be absolutely essential for translocation of CagA into host cells and 14 out of 27 for the ability of Hp fully to induce transcription of IL‐8. The products of hp0524 (virD4 homologue), hp0526 and hp0540 are absolutely essential for the translocation of CagA, but not for the induction of IL‐8. In contrast, the products of hp0520, hp0521, hp0534, hp0535, hp0536 and hp0543 are not necessary for either translocation of CagA or for IL‐8 induction. Our data argue against a translocated IL‐8‐inducing effector protein encoded by the cag‐PAI. We isolated a variant of Hp 26695, which spontaneously switched off its capacity for IL‐8 induction and translocation of CagA, but retained the complete cag‐PAI. We identified a point mutation in gene hp0532, causing a premature translational stop in the corresponding polypeptide chain, providing a putative explanation for the defect in the type IV secretion system of the spontaneous mutant.

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Metadata

Authors
Fischer, W., Püls, J., Buhrdorf, R., Gebert, B., Odenbreit, S., & Haas, R.
Venue
Molecular Microbiology
Publisher
Wiley
Published
2001-12
Volume
42
Issue
5
Pages
1337-1348
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
OpenAlex
W2087327203
Cited by
508
References
37
FWCI
23.29
Type
journal article
Language
en
Open access
bronze

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Fischer, W., Püls, J., Buhrdorf, R., Gebert, B., Odenbreit, S., & Haas, R. (2001). Systematic mutagenesis of the Helicobacter pylori cag pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin‐8. Molecular Microbiology. https://doi.org/10.1046/j.1365-2958.2001.02714.x

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