Mosaicism in Vacuolating Cytotoxin Alleles of Helicobacter pylori
ASSOCIATION OF SPECIFIC vacA TYPES WITH CYTOTOXIN PRODUCTION AND PEPTIC ULCERATION (*)
- John C. Atherton(1),
- Ping Cao(1),
- Richard M. Peek, Jr.(2),
- Murali K. R. Tummuru(1),
- Martin J. Blaser(1)(3) and
- Timothy L. Cover(1)(3)(§)
- From the (1) Divisions of Infectious Disease and
- (2) Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605 and the
- (3) Department of Veterans Affairs Medical Center, Nashville, Tennessee 37232-2637
- § To whom correspondence should be addressed: Division of Infectious Diseases, Medical Center North A3310, Vanderbilt University School of Medicine, Nashville, TN 37232-2605. Tel.: 615-322-2035; Fax: 615-343-6160.
Abstract
Approximately 50% of Helicobacter pylori strains produce a cytotoxin, encoded by vacA, that induces vacuolation of eukaryotic cells. Analysis of a clinically isolated tox
strain (Tx30a) indicated secretion of a 93-kDa product from a 3933-base pair vacA open reading frame. Characterization of 59 different H. pylori isolates indicated the existence of three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). All possible combinations
of these vacA regions were identified, with the exception of s2/m1 (p < 0.001); this mosaic organization implies that recombination has occurred in vivo between vacA alleles. Type s1/m1 strains produced a higher level of cytotoxin activity in vitro than type s1/m2 strains; none of 19 type s2/m2 strains produced detectable cytotoxin activity. The presence of cagA (cytotoxin-associated gene A) was closely associated with the presence of vacA signal sequence type s1 (p < 0.001). Among patients with past or present peptic ulceration, 21 (91%) of 23 harbored type s1 strains compared with 16
(48%) of 33 patients without peptic ulcers; only 2 (10%) of 19 subjects harboring type s2 strains had past or present peptic
ulcers (p < 0.005). Thus, specific vacA genotypes of H. pylori strains are associated with the level of in vitro cytotoxin activity as well as clinical consequences.
Footnotes
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↵* This work was supported in part by National Institutes of Health Grants R29 DK45293 and R01 CA58834, the Medical Research Service of the Department of Veterans Affairs, and a Pfizer Scholars Award. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- bp
-
base pair(s)
- PCR
-
polymerase chain reaction
- ELISA
-
enzyme-linked immunosorbent assay
- kb
-
kilobase pair(s).
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- Received March 14, 1995.
- Revision received May 15, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
