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Living dangerously: how Helicobacter pylori survives in the human stomach

Nature Reviews Molecular Cell Biology volume 2, pages 457–466 (2001)Cite this article

Key Points

  • Helicobacter pylori is a human-specific pathogen that resides in the stomach. To adapt, survive and proliferate in such environment, this bacterium has elaborated a unique set of virulence factors. The study of their mode of action is unravelling novel aspects of bacterial physiology and, at the same time, of our own physiology, and of the inflammatory and immune response.

  • The continuing research has highlighted the role of the following molecules: a powerful urease; flagellar proteins; a H-gated urea transporter; several adhesins; a vacuolating toxin that causes several specific cellular alterations that seem to be functional for the survival of the bacterium; and bacterial factors that activate inflammatory cells either directly or indirectly through inducing the tissue cells to release pro-inflammatory cytokines.

  • Research is being done to develop vaccines based on studies of modified or unmodified virulence factors. The hope is to be able to prevent or eradicate infection.

Abstract

Helicobacter pylori was already present in the stomach of primitive humans as they left Africa and spread through the world. Today, it still chronically infects more than 50% of the human population, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. To succeed in these long-term associations, H. pylori has developed a unique set of virulence factors, which allow survival in a unique and hostile ecological niche — the human stomach.

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Figure 1: Schematic representation of the stomach mucosa colonized by Helicobacter pylori, showing the main virulence factors involved in colonization and disease.
Figure 2: Helicobacter pylori.
Figure 3: Scheme of the intracellular events involved in the HP-NAP activation of human leukocytes.
Figure 4: Current model of the cellular alterations induced by VacA cytotoxin.
Figure 5: The secretion system of Helicobacter pylori injects bacterial proteins into the cytosol of host cells.

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Acknowledgements

We apologize to the authors of the many relevant papers that we could not quote owing to space limitations. We thank A. Covacci, M. de Bernard, G. Del Giudice, W. Dundon, E. Papini, J. L. Telford and M. Zoratti for many discussions and for critical reading of the manuscript, and to G. Corsi for the artwork. Work carried out in the authors' laboratories was supported by European Community grants, by the CNR–MURST 5% Project, by MURST 40% Projects on Inflammation and by the Armenise–Harvard Medical School Foundation.

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  1. Centro CNR Biomembrane e Dipartimento di Scienze Biomediche, Università di Padova, Via G. Colombo 3, Padova, 35121, Italy

    Cesare Montecucco & Rino Rappuoli

  2. Centro di Ricerche IRIS, Chiron S.p.A., Via Fiorentina, 1, 53100, Siena, Italy

    Cesare Montecucco & Rino Rappuoli

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IL-8

GRO

epithelial-derived neutrophil-activating protein 78

RANTES

metaphase chromosome protein 1

Rab7

cytochrome c

cagA

NF-κB

AP1

phospholipase A2

mitogen-activated protein kinase

p21-activated kinase

MHC class I

FURTHER INFORMATION

The complete sequences of two strains of H. pylori (J99 and 26695)

A yeast two-hybrid protein–protein interaction map

Glossary

GRAM-NEGATIVE BACTERIA

Bacteria whose cell walls do not retain a basic blue dye during the Gram-stain procedure. These cell walls are thin, consisting of a layer of lipopolysaccharide outside a peptidoglycan layer.

ADENOCARCINOMA

Cancer originating from uncontrolled proliferation of epithelial cells of the ducts and acini of glandular organs.

LYMPHOMA

Cancer originating from uncontrolled proliferation of lymphocytes.

MUCUS

Slimy substance secreted by mucous cells of the mucosae that consists predominantly of mucins — highly glycosylated proteins of high molecular weight. The function of mucus is to protect the linings of body cavities.

LEWIS ANTIGEN

A system of soluble antigens in secretions and plasma that represents one of the serologically distinguishable human blood-group substances. Lewis specificities are carried on glycosphingolipids and glycoproteins.

PERIPLASM

Space between the outer and the inner membranes of Gram-negative bacteria.

NEUTROPHIL

A phagocytic cell of the myeloid lineage that has an important role in the inflammatory response, undergoing chemotaxis towards sites of infection or wounding.

MYELOPEROXIDASE

Peroxidase from neutrophils that takes part in the bactericidal activity of these cells. The name originates from the first isolation from the blood of patients with myeloid leukaemia.

MONOCYTE

Large leukocytes with a horseshoe-shaped nucleus. They derive from pluripotent stem cells and become phagocytic macrophages when they enter the tissues.

PROINFLAMMATORY CYTOKINES

Secreted proteins with autocrine or paracrine action that regulate the inflammatory response. There are many types of cytokine, which elicit different cellular responses including control of cell proliferation and differentiation, regulation of immune responses and haematopoiesis.

EPITHELIAL CELLS

Polarized cells that cover the outer surfaces of the body and line internal cavities or tubes (except blood vessels).

OXYNTIC CELLS

Cells of the gastric mucosa that secrete hydrochloric acid.

PERISTALSIS

A wave-like sequence of contraction and relaxation that passes along a tube-like structure, resulting in a net forward movement of the content.

LECTIN

Agglutinins and other antibody-like proteins of nonimmune origin that bind sugars.

ENDOTHELIAL CELLS

Flattened cells that grow in a single layer and line blood vessels.

LPS

(Lipopolysaccharide.) Components of the outer membrane of Gram-negative bacteria that are made of a lipid, a core oligosaccharide and an O-linked sugar side chain.

CHEMOKINE

A type of chemotactic cytokine that acts primarily on haematopoietic cells in acute and inflammatory processes.

FIBRINOLYSIS

The proteolysis of fibrin by plasmin in blood clots.

TISSUE FACTOR

A transmembrane glycoprotein that initiates blood coagulation.

TRANS-EPITHELIAL RESISTANCE

Electric resistance across epithelial sheets, measured across the apical–basolateral axis of the cell.

TIGHT JUNCTION

A belt-like region of adhesion between adjacent epithelial or endothelial cells. Tight junctions regulate paracellular flux, and contribute to the maintenance of cell polarity by stopping molecules from diffusing within the plane of the membrane.

APICAL SURFACE

Surface of an epithelial or endothelial cell that faces the lumen of a cavity or tube, or the outside of the organism.

ANTIGEN-PRESENTING CELLS

Cells specialized in the generation of epitopes that are presented through major histocompatibility complex II (MHC II) to T lymphocytes.

CD4+ T CELLS

T helper cells, which collaborate with antigen-presenting cells in the initiation of an immune response.

CD8+ CYTOTOXIC TCELLS

T cytotoxic cells, which are directly responsible for killing cells that present peptides through MHC I.

TRANSPOSABLE ELEMENTS

Also called transposons. Specific DNA sequences that are transferred as a unit from one replicated DNA sequence to another.

HORIZONTAL TRANSFER

Transfer of DNA sequences from one bacterium to another.

COMMENSAL

Either of two species that live in close association with benefit to one partner but with little or no effect on the other partner.

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Montecucco, C., Rappuoli, R. Living dangerously: how Helicobacter pylori survives in the human stomach. Nat Rev Mol Cell Biol 2, 457–466 (2001). https://doi.org/10.1038/35073084

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