Virulence Mechanisms and Persistence Strategies of the Human Gastric Pathogen Helicobacter pylori

Chapter

Abstract

The human gastric pathogen Helicobacter pylori is able to establish an infection in a hostile environment with virtually no competitors. For this purpose, it has elaborated a set of colonization factors which facilitate both survival under acid exposure, motility and orientation in a highly viscous mucus layer, and adherence to epithelial surfaces. A more intimate interaction with gastric epithelia provides the basis to influence gene expression profiles as well as morphological transitions via signaling cascades or via direct activities of virulence factors. H. pylori is also one of the most genetically diverse of organisms, and variations are not only found in outer membrane adhesins, but also in two major virulence factors, the VacA cytotoxin and the cag pathogenicity island. Both factors are able to target different cell types and different interaction partners to induce a wide range of possible cellular effects. Despite the fact that H. pylori elicits a strong inflammatory response, the immune system fails to clear the infection, suggesting that immune evasion strategies are used. The mechanisms for immune evasion include the induction of a strongly polarized immune response, a modulation of phagocytosis and neutrophil function, and an inhibition of lymphocyte proliferation. Prolonged inflammation and direct action of bacterial factors may lead to impairment of gland function and eventually to carcinogenesis.

Abbreviations

DC-SIGN

Dendritic cell-specific ICAM-3-grabbing nonintegrin

EGFR

Epidermal growth factor receptor

FAK

Focal adhesion kinase

GSK

Glycogen synthase kinase

IL

Interleukin

iNOS

Inducible nitric oxide synthase

JNK

Jun N-terminal kinase

Leb

Lewis b

LPS

Lipopolysaccharide

MALT

Mucosa-associated lymphoid tissue

MMP

Matrix metalloproteinase

NFAT

Nuclear factor of activated T cells

PAI

Pathogenicity island

PI3K

Phosphatidylinositol-3-kinase

PKC

Protein kinase C

PMA

Phorbol-myristate-acetate

PMN

Polymorphonuclear cell

ROS

Reactive oxygen species

sLex

Sialyl-Lewis x

T4SS

Type IV secretion system

TLR

Toll-like receptor

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Max von Pettenkofer-Institut für Hygiene und Medizinische MikrobiologieLudwig-Maximilians-Universität MünchenMünchenGermany

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