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Anar Dossumbekova, Christian Prinz, Jörg Mages, Roland Lang, Johannes G. Kusters, Arnoud H. M. Van Vliet, Wolfgang Reindl, Steffen Backert, Dieter Saur, Roland M. Schmid, Roland Rad, Helicobacter pylori HopH (OipA) and Bacterial Pathogenicity: Genetic and Functional Genomic Analysis of hopH Gene Polymorphisms, The Journal of Infectious Diseases, Volume 194, Issue 10, 15 November 2006, Pages 1346–1355, https://doi.org/10.1086/508426
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Abstract
BackgroundExpression of the Helicobacter pylori outer membrane protein HopH is regulated by phase variation within a CT dinucleotide repeat motif of the hopH gene
MethodsTo investigate the importance of HopH for bacterial pathogenicity, we performed a detailed functional genomic and population-based genetic characterization of this contingency locus
ResultsSequencing of hopH in H. pylori strains from 58 patients revealed that the hopH “on” genotype is linked to bacterial virulence determinants, such as the vacAs1, vacAm1, babA2 and, most strongly, cagA genotypes. hopH mutagenesis resulted in reduced bacterial adherence to gastric epithelia in vitro. Complementation of hopH in trans restored the adherence properties of hopH mutants. Although HopH has been previously linked to proinflammatory epithelial signaling, hopH mutagenesis did not alter epithelial interleukin-8 secretion in vitro. Comparative epithelial gene-expression profiling by cDNA microarrays revealed no significant differences between the wild-type–specific and hopH mutant–specific transcriptomes. By contrast, a large set of genes was differentially regulated in a cag pathogenicity island–dependent manner
ConclusionAn in-frame hopH gene may be linked to gastroduodenal diseases because of its association with other virulence factors or increased bacterial adherence and colonization. The strong linkage with cagA indicates that HopH may contribute to the fitness of cagA-positive strains in vivo