| Literature References | 1. CENSINI, S., LANGE, C., XIANG, Z., CRABTREE, J.E., GHIARA, P.,
BORODOVSKY, M., RAPPUOLI, R. AND COVACCI, A.
Cag, a pathogenicity island of Helicobacter pylori, encodes type-1-specific
and disease-associated virulence factors.
PROC.NATL.ACAD.SCI.U.S.A. 93 14648-14653 (1996).
2. CHRISTIE, P.J. AND VOGEL, J.P.
Bacterial type IV secretion: conjugation systems adapted to deliver effector
molecules to host cells.
TRENDS MICROBIOL. 8 354-367 (2000).
3. ASAHI, M., AZUMA, T., ITO, S., ITO, Y., SUTO, H., NAGAI, Y., TSUBOKAWA,
M., MAEDA, S., OMATA, M., SUZUKI, T. AND SASAKAWA, C.
Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric
epithelial cells.
J.EXP.MED. 191 593-602 (2000).
4. COVACCI, A. AND RAPPUOLI, R.
Tyrosine-phosphorylated bacterial proteins: trojan horses for the host cell.
J.EXP.MED. 191 587-592 (2000).
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| Documentation | Helicobacter pylori is a Gram-negative flagellated pathogen that causes
gastric and peptic ulcers. In its chronic state, it can also contribute to
gastric cancer development, through elicitation of a huge host inflammatory
response [1]. It has been suggested that activated leukocytes may be
responsible for tissue damage, and that phagocytes contribute to
carcinogenesis. The Helicobacter genome contains several virulence factors;
clinical strains may be divided roughly into two types, depending on
whether they contain the functional cag pathogenicity island. Type I strains
can cause malignant disease, as they possess the active cag island and
its associated exotoxin, CagA.
The bacterium makes use of a type IV secretion system similar in mechanism
to the conjugation machine of Agrobacterium tumefaciens [2]. These machines
secrete three different types of substrate: DNA conjugation intermediates,
as in A.tumefaciens; multimeric proteins, such as the pertussis toxin of
Bordetella pertussis; and the CagA protein of H.pylori [3]. CagA has been
linked to the more severe forms of gastric ulcers and duodenal cancers [3].
Both CagA and the secretion system apparatus are encoded in the large
pathogenicity island, termed cag [3], possessed by the malignant disease-
causing type I bacterial strains.
The CagA exotoxin is encoded in the last portion of the island, and
mutants lacking the gene fail to induce IL-8 secretion, and to activate
NF-kappa-B in vivo [4]. CagA is believed to have a similar function to
EPEC type III secreted effectors; both are tyrosine-phosphorylated once
translocated into the target cell [4], and allow engulfment by the host via
rearrangement of the actin cytoskeleton.
TYPE4SSCAGA is an 11-element fingerprint that provides a signature for the
type IV secretion system CagA exotoxin family. The fingerprint was derived
from an initial alignment of 8 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length (~1266
amino acids). A single iteration on SPTR39_14f was required to reach
convergence, no further sequences being identified beyond the starting set.
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