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Clinical and Diagnostic Laboratory Immunology, March 1998, p. 139-145, Vol. 5, No. 2
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

vacA Genotypes and Genetic Diversity in Clinical Isolates of Helicobacter pylori

Shan-Rui Han, Hans-Joachim Schreiber, Sucharit Bhakdi, Michael Loos, and Markus J. Maeurer*

Department of Medical Microbiology, Johannes Gutenberg University, D-55101 Mainz, Germany

Received 14 April 1997/Returned for modification 26 June 1997/Accepted 15 December 1997

Genetic diversity in Helicobacter pylori strains may affect the function and antigenicity of virulence factors associated with bacterial infection and, ultimately, disease outcome. In this study, DNA diversity of H. pylori isolates was examined by analysis of vacA genotypes and by restriction fragment length polymorphism (RFLP) analysis of H. pylori-associated genes (vacA, cagA, flaA, ureAB, and ureCD). Thirty-seven H. pylori isolates from 26 patients were successfully classified into distinct vacA allelic genotypes. The signal sequence allele s1 (31 of 37) predominated over the s2 allele (6 of 37) and was significantly associated with the occurrence (past or present) of gastric ulcers. A novel midregion allele, designated as m3, has been identified in two H. pylori isolates which could not be typed with midregion allele m1- or m2-specific primers. Additionally, significant nucleotide diversity yielding different amino acid sequences was demonstrated by DNA sequencing of vacA fragments from clinical isolates of H. pylori. Furthermore, RFLP analysis of 45 H. pylori isolates (including 15 paired isolates) obtained from antrum and corpus biopsy specimens from 30 individual patients showed remarkably high interhost diversity (one patient, one H. pylori strain) and intrahost identity in gene sequences coding for VacA, CagA, flagellin, and urease. Only in a single patient was a minor genotypic variation at different anatomic sites within the stomach identified. These data warrant the detailed analysis of the effect of genetic diversity on the function and antigenicity of H. pylori-associated virulence factors.

* Corresponding author. Mailing address: Department of Medical Microbiology, Johannes Gutenberg University, Hochhaus/Augustusplatz, D-55101 Mainz, Germany. Phone: (49) 6131-177341. Fax: (49) 6131-173439. E-mail: maeurer{at}omalley.zdv.uni-mainz.de.

Clinical and Diagnostic Laboratory Immunology, March 1998, p. 139-145, Vol. 5, No. 2
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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