Helicobacter pylori HopH (OipA) and Bacterial Pathogenicity: Genetic and Functional Genomic Analysis of hopH Gene Polymorphisms

• Published in: The Journal of infectious diseases Vol. 194; no. 10; pp. 1346 - 1355
• Main Authors: Dossumbekova, Anar, Prinz, Christian, Mages, Jörg, Lang, Roland, Kusters, Johannes G., Van Vliet, Arnoud H. M., Reindl, Wolfgang, Backert, Steffen, Saur, Dieter, Schmid, Roland M., Rad, Roland
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 15-11-2006; University of Chicago Press
• Subjects: Adhesins, Bacterial - genetics; Amino Acid Sequence; Antigens, Bacterial - genetics; Antigens, Bacterial - metabolism; Bacteria; Bacterial adhesion; Bacterial Adhesion - genetics; Bacterial colonization; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - physiology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Cell Line, Tumor; Cell lines; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; Epithelial cells; Gastric Mucosa - metabolism; Gastric Mucosa - microbiology; Gene Expression Profiling; Genetic Complementation Test; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Humans; Infections; Interleukin-8 - biosynthesis; Membrane proteins; Molecular Sequence Data; Mutagenesis; Oligonucleotide Array Sequence Analysis; Polymorphism, Genetic; RNA, Messenger - analysis; Secretion; Sequence Alignment; Virulence - genetics; Virulence factors
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/508426

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