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2 authors:
Luigina Cellini
Gianfranco Donelli
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ORIGINAL ARTICLE
INTRODUCTION
Helicobacter pylori colonizes the human stomach early in
life even if only decades later the related pathology may be
expressed. Both the spiral-shaped bacterium and its coccoid form (1 5) persist in a unique biological niche within
the gastric mucus layer (6) and are able to cause a strong
inammatory state and lesions of the gastric mucosa (7)
and to drive a relevant immune response in a restricted
percentage of hosts (8, 9). In fact, disease occurs only in
about 15% of people infected, with the development of
gastritis, gastric glandular athrophy, duodenal and gastric
ulcers, gastric adenocarcinoma or MALT lymphoma (10).
Genomic and phenotipic features of different strains, presumably together with the transient condition of the gastric microenvironment, allow the expression of virulence
factors which enable some strains, rather than others, to
cause disease (7, 10). H. pylori expresses its pathogenicity
through: (i) adhesion to gastric epithelium; (ii) colonization of the mucous gel layer increasing the permeability to
hydrogen ions and pepsin; (iii) penetration in and distruction of intercellular junctions; (iv) invasion of gastric
glands and canaliculi of parietal cells; (v) evasion of host
immune defences; (vi) secretion of enzymes and production
of cytotoxins (11).
Several virulence factors (Table I) contribute to the
pathogenicity of H. pylori.
UREASE
Urease is an important virulence factor for H. pylori and is
critical for bacterial colonization of the human gastric
Taylor & Francis 2000. ISSN 1403-4174
mucosa. H. pylori urease metabolizes urea producing ammonia to neutralise the microenvironment in which the
bacterium resides (12). The presence of cytoplasmatic urease activity suggests a role of this enzyme in assimilation
of organic nitrogen (12, 13). The ammonia production can
damage the gastric mucosa through the disruption of tight
junctions and the alteration of permeability of gastric
epithelium. Moreover, urease stimulates activation of
mononuclear phagocytes and production of inammatory
cytokines (14). The native H. pylori urease consists of a
nickel-containing hexameric molecule with a molecular
mass of approximately 540 kDa made up of two subunits:
UreA [30 kDa] and UreB [62 kDa]. The urease gene
cluster contains nine genes, including ureA and ureB structural genes (15).
PHOSPHOLIPASES
H. pylori phospholipases induce generation of products
such as lysolecithin which disrupt the protective phospholipid-rich layer on the apical membrane of mucus cells
(16).
FLAGELLA
The presence of agella is an essential factor of colonization in H. pylori. Aagellate strains are not able to colonize gnotobiotic piglets (17). H. pylori possesses two to six
polar agella characterized by two types of agellin
proteins coded by aA and aB genes that are required for
full motility and persistent infection of the gastric mucosa
(18). A recent study demonstrated that agellar biosynthesis and urease activity may be linked (19).
Microbial Ecology in Health and Disease
260
Table I
Virulence factors of Helicobacter pylori
Factor
Gene
Function
Urease
ure operon
Phospholipase
Flagella
Nap
Adhesins
IceA
VacA
cag PAI
gene
flaA, aB
napA
babA1, babA2
iceA1, iceA2
vacA
31 genes coding for type IV secretion system
CagA
H. pylori virulence
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