CagA VagA toxins are released and remain attached to

CagA Pathogenicity Island is a region in the H
pylori genome consisting of 40kb. It consist of 31 potential coding region
which are homologous to genes of other bacteria species and encodes for
different types of Type IV Secretary Systems (T4SS)12656466. This T4SS is very important in the attainment of
virulence by H pylori because the translocation of CagA proteins, peptidoglycan
and other bacteria factors into the host cells is dependent on some of its
components which form syringe-like structures67682169. Some of these T4SS components also confer
virulence through the modulation of host immune responses to suite bacterial
persisting hence augmenting host inflammatory responses. CagA

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CagA gene is a gene that encodes for a 140kDa CagA
protein and it acts a marker for Cagpai. H pylori strains are known to be CagA-
(no CagA PI) which are less virulent and the more virulent CagA+ strain (with
cagpai). Once injected into the host cells, host cell kinases phosphorylates
the tyrosine residues of these cagA protein which then interact with host
proteins responsible for cell growth, cell motility and cell polarity hence
causing morphological and hence functional changes of the epithelial cells69. This interaction between cagA and host proteins
is achieved by cagA phosphorylation dependent and phosphorylation-independent
mechanisms316320. Phosphorylated cagA protein also stimulates increase
IL-8 expression, a pro-inflammatory cytokine resulting in pronounce
inflammatory response and cytoskeletal rearrangement which may lead to gastric
cancer7071. VagA gene.

H pylori vagA gene found in almost all strains  with a high degree of allelic diversity encodes
for the vagA vacuolating cytotoxin, a 95kDa protein which is highly immunogenic
and stimulates enormous vacuolation in epithelial cells in vitro727374. Upon entry into the host cell, the VagA toxins
are released and remain attached to the host cell surface receptors where they
engage in the formation of membrane channels, endosomal disruption,
interference of cytoskeleton dependent cell functions, induction of apoptosis
and modification of host immune responses7576. These membrane channels causes the release of urea,
anions, nutrients and cations from host cell hence disrupting cell integrity
and contributing to the pathogenesis of peptic ulcer diseases7778.  Duodenal
ulcer promoting gene (dupA)

dupA gene located in the plasticity region of H
pylori genome encodes for the dupA protein, a virulence factor which has been
found to be associated with increase expression levels of IL-8 and other CD14+
mononuclear pro-inflammatory cytokines such as IL-12p40, IL-12p70 and IL-2379808182. These observation suggests the involvement of the
dupA gene in gastric inflammation. There are controversial studies about the
dupA involvement H pylori pathogenesis and it has been attributed to the
diversity of the dupA and the fact that many studies failed to consider vir genes
adjacent to the dupA which is also needed for its function 79. More studies is needed for the characterisation
this virulence factor.
by contact with epithelial gene

It consist of a virulent iceA1 and and virulent iceA2
allelic variants. IceA1 are upregulated upon H pylori contact with gastric
epithelial cells and it encodes for a CTAG- specific restriction endonuclease,
a homologue of nlaIIIR which a Neisseria lactamica gene8382. Some studies showed the association of iceA1 with
peptic ulcer diseases and increase stimulation of IL-88485. Its action is independent of vagA and cagA levels
but the role of its endonuclease activities is yet to be established.

1.5.2.      H pylori Enzymes. Urease

In order to successfully colonise and persist in
the stomach mucosa, H pylori produces urease, an enzyme which hydrolysis urea
to ammonia and carbon dioxide. The excess ammonia produced buffers the acidic pH
of the stomach and also forms carcinogenic agents together with neutrophils
metabolites, a potential cause of gastric cancers86878889. Urease also induces inflammation through the
production of pro-inflammatory cytokines and the recruitments of neutrophils
and monocytes in the stomach mucosa90. Catalase.

Catalase is an enzyme with a recyclable oxidizable
methionine residue used to quench the oxidant hydrogen peroxide. H pylori
produces catalase as a defence tragedy against host mediated oxidative stress and
other harmful oxidants through this recyclable methionine hence increasing
colonization and persistence91.


expressed on the surface of H pylori aids in immune evasion and subsequent
colonisation of the host due to the presence of fucosylated oligosaccharide
antigen (bacterial Lewis antigen) on its O-specific chain92. This bacterial Lewis is known to act as a mimic
to the closely related human Lewis antigen hence causing persistence and
possible autoimmune responses leading to increase virulence12. 

HOPs Adhesins

In order to obtain stability against mucosal
moulting in the gastric lumen, H pylori expresses various types of outer
membrane proteins known as Hop adhesins which have specific receptors on the
surface of gastric epithelial cells. These adhesins are not only implicated in
attachment but helps the bacterium to have good access to nutrients released
from damaged epithelial cells69. Sialic acid-binding adhesion (SabA

SabA is a 70kDa adhesion protein which binds
sialylated dimeric lewis x antigen through a selection-mimicry mechanism on the
surface of mucosa epithelial cells826993. Sialylation of lewis antigen to sialylated lewis
antigen x is known to occurs increasingly during chronic tissue inflammation
and carcinomas, suggesting the role of SabA in these disease states and
maintenance of colonisation9495. Sialylated carbohydrates are also found on the
surface of granulocytes which binds SabA leading to oxidative stress on the
cells96. Moreso, SabA is also implicated in haem
agglutination through its binding to siLex a ntigens on the surface of red
blood cells96 membrane inflammatory
proteins (OipA)

OipA also known as HopH is a 34kDa protein with a
pro-inflammatory function achieved through the phosphorylation of cagPAI
associated signalling pathways6421. Its function was evident as increase mucosa IL-8
expression rate together with enormous neutrophils infiltration were observed
to be concomitant with OipA. More so, 70% of chronic gastritis cases were found
harbouring this protein as compared to 95.5% of duodenal cancer cases82



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