Báo cáo khoa học: Assembly and molecular mode of action of the Helicobacter pylori Cag type IV

MINIREVIEW

Assembly and molecular mode of action of the

Helicobacter pylori Cag type IV secretion apparatus

Wolfgang Fischer

Max von Pettenkofer-Institut, Ludwig-Maximilians-Universita¨t, Mu¨nchen, Germany

Introduction

Type IV secretion systems (T4SS) represent a family of

macromolecule transporters that is widely distributed

in prokaryotes, and individual members of this family

have adapted to their cellular background and to a

variety of substrates as DNA import and export sys￾tems, conjugation systems or effector protein translo￾cation systems [1]. Several pathogenic bacteria have

adopted T4SS for the secretion of virulence-associated

proteins to the extracellular milieu or for their injec￾tion into different host cells, mediating host cell

manipulation in different ways and thereby facilitating

mucosa-associated or intracellular lifestyles. The

human gastric pathogen Helicobacter pylori, which is

the principal cause of chronic active gastritis and pep￾tic ulcer disease, and also is involved in the develop￾ment of mucosa-associated lymphoid tissue lymphoma

and gastric cancer [2], uses different T4SS for horizon￾tal gene transfer, and the cytotoxin-associated gene

(Cag) T4SS for interactions with various host cells

[3,4]. The Cag-T4SS is encoded on the cytotoxin-asso￾ciated gene-pathogenicity island (cagPAI), a 37 kb

genomic island representing one of the major variable

genome regions of H. pylori that is clearly associated

with an enhanced risk of developing peptic ulcers or

adenocarcinoma. The percentage of cagPAI-positive

strains varies considerably between geographically dis￾tinct groups, ranging from universal presence in East

Asian isolates to a complete absence in certain African

populations [5]. Strains carrying the cagPAI are often

equipped with a vacuolating cytotoxin (vacA) s1 ⁄ m1

genotype, suggesting a common selective pressure for

these two major virulence factors, and have been

Keywords

CagA; Helicobacter pylori; pathogenicity

island; protein translocation; secretion

apparatus; type IV secretion

Correspondence

W. Fischer, Max von Pettenkofer-Institut,

Ludwig-Maximilians-Universita¨t,

Pettenkoferstrasse 9a, 80336 Mu¨nchen,

Germany

Fax: +49 89 51605223

Tel: +49 89 51605277

E-mail: [email protected]

(Received 15 November 2010, accepted

10 January 2011)

doi:10.1111/j.1742-4658.2011.08036.x

Bacterial type IV secretion systems (T4SS) form supramolecular protein

complexes that are capable of transporting DNA or protein substrates

across the bacterial cell envelope and, in many cases, also across eukaryotic

target cell membranes. Because of these characteristics, they are often used

by pathogenic bacteria for the injection of host cell-modulating virulence

factors. One example is the human pathogen Helicobacter pylori, which

uses the Cag-T4SS to induce a pro-inflammatory response and multiple

cytoskeletal and gene regulatory effects in gastric epithelial cells. Work in

recent years has shown that the Cag-T4SS exhibits marked differences in

relation to other systems, both with respect to the composition of its secre￾tion apparatus and the molecular details of its secretion mechanisms. This

review describes the molecular properties of the Cag-T4SS and compares

these with prototypical systems of this family of protein transporters.

Abbreviations

cagPAI, cytotoxin-associated gene-pathogenicity island; IL, interleukin; T4SS, type IV secretion system.

FEBS Journal 278 (2011) 1203–1212 ª 2011 The Author Journal compilation ª 2011 FEBS 1203