DOI: 10.1128/iai.02025-05. The Novel <i>Helicobacter pylori</i> CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization

The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization

10.1128/iai.02025-05

Crossref journal-article

American Society for Microbiology

Infection and Immunity (235)

Abstract

ABSTRACT Maintaining metal homeostasis is crucial for the adaptation of Helicobacter pylori to the gastric environment. Iron, copper, and nickel homeostasis has recently been demonstrated to be required for the establishment of H. pylori infection in animal models. Here we demonstrate that the HP0969-0971 gene cluster encoding the Czc-type metal export pump homologs HP0969, HP0970, and the H. pylori -specific protein HP0971 forms part of a novel H. pylori metal resistance determinant, which is required for gastric colonization and for the modulation of urease activity. Insertional mutagenesis of the HP0971, HP0970, or HP0969 genes in H. pylori reference strain 26695 resulted in increased sensitivity to cadmium, zinc, and nickel (czn), suggesting that the encoded proteins constitute a metal-specific export pump. Accordingly, the genes were designated cznC (HP0971), cznB (HP0970), and cznA (HP0969). The CznC and CznA proteins play a predominant role in nickel homeostasis, since only the cznC and cznA mutants but not the cznB mutant displayed an 8- to 10-fold increase in urease activity. Nickel-specific affinity chromatography demonstrated that recombinant versions of CznC and CznB can bind to nickel and that the purified CznB protein interacted with cadmium and zinc, since both metals competitively inhibited nickel binding. Finally, single cznA , cznB , and cznC mutants did not colonize the stomach in a Mongolian gerbil-based animal model. This demonstrates that the metal export functions of H. pylori cznABC are essential for gastric colonization and underlines the extraordinary importance of metal ion homeostasis for the survival of H. pylori in the gastric environment.

Bibliography

StaÌhler, F. N., Odenbreit, S., Haas, R., Wilrich, J., Vliet, A. H. M. V., Kusters, J. G., Kist, M., & Bereswill, S. (2006). The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization. Infection and Immunity, 74(7), 3845â3852.

Authors 8

Frank Nils Stähler (first)
Stefan Odenbreit (additional)
Rainer Haas (additional)
Julia Wilrich (additional)
Arnoud H. M. Van Vliet (additional)
Johannes G. Kusters (additional)
Manfred Kist (additional)
Stefan Bereswill (additional)

References 42 Referenced 120

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Dates

Type	When
Created	19 years, 2 months ago (June 21, 2006, 7:10 p.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 1:38 a.m.)
Indexed	2 weeks, 4 days ago (Aug. 6, 2025, 8:59 a.m.)
Issued	19 years, 1 month ago (July 1, 2006)
Published	19 years, 1 month ago (July 1, 2006)
Published Print	19 years, 1 month ago (July 1, 2006)

Funders 0

None

BibTeX

@article{Sta_hler_2006, title={The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization}, volume={74}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.02025-05}, DOI={10.1128/iai.02025-05}, number={7}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Stähler, Frank Nils and Odenbreit, Stefan and Haas, Rainer and Wilrich, Julia and Vliet, Arnoud H. M. Van and Kusters, Johannes G. and Kist, Manfred and Bereswill, Stefan}, year={2006}, month=jul, pages={3845–3852} }

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    },
    {
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        "name": "publication_history",
        "label": "Publication History"
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    },
    {
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      "order": 2,
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        "name": "publication_history",
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  ]
}