Abstract
BackgroundThe homB gene is a Helicobacter pylori disease-marker candidate, strongly associated with peptic ulcer disease, while homA, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia. The HomB encoded outer membrane protein was shown to contribute to the proinflammatory properties of H. pylori and also to be involved in bacterial adherence.This study investigated the distribution of homB and homA genes in 455 H. pylori strains from East Asian and Western countries, and carried out sequence comparison and phylogenetic analyses.ResultsBoth homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains.Analysis of homB and homA sequences revealed diversity regarding the number of copies and their genomic localization, with East Asian and Western strains presenting different genotypes. Moreover, homB and homA sequence analysis suggests regulation by phase variation. It also indicates possible recombination events, leading to gene duplication or homB/homA conversion which may as well be implicated in the regulation of these genes. Phylogenetic reconstruction of homB and homA revealed clustering according to the geographic origin of strains. Allelic diversity in the middle region of the genes was observed for both homB and homA, although there was no correlation between any allele and disease. For each gene, a dominant worldwide allele was detected, suggesting that homB/homA allelic variants were independent of the geographical origin of the strain. Moreover, all alleles were demonstrated to be expressed in vivo.ConclusionOverall, these results suggest that homB and homA genes are good candidates to be part of the pool of H. pylori OMPs implicated in host-bacteria interface and also contributing to the generation of antigenic variability, and thus involved in H. pylori persistence.
Highlights
The homB gene is a Helicobacter pylori disease-marker candidate, strongly associated with peptic ulcer disease, while homA, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia
H. pylori infection is implicated in the development of several gastroduodenal diseases, ranging from chronic active gastritis and dyspepsia to peptic ulcer disease (PUD), and associated with an increased risk for gastric cancer [1]
The virulence of the infecting strain influences the severity of the clinical outcome, and disease associations have been proposed for the cag pathogenicity island (PAI), vacA and several genes encoding outer membrane proteins (OMP) [2,3,4,5,6,7]
Summary
The homB gene is a Helicobacter pylori disease-marker candidate, strongly associated with peptic ulcer disease, while homA, its paralogue gene with 90% sequence identity, is correlated with non-ulcer dyspepsia. The virulence of the infecting strain influences the severity of the clinical outcome, and disease associations have been proposed for the cag pathogenicity island (PAI), vacA and several genes encoding outer membrane proteins (OMP) [2,3,4,5,6,7]. Bacterial factors which modulate interactions with human cells, such as OMPs, have been involved in the pathophysiology of the infection caused by H. pylori. These proteins can contribute to the colonization and persistence of H. pylori, as well as influence the disease process [5,6,7]. The disease can develop earlier, and rare cases have been observed in children, suggesting that the H. pylori strains involved are more virulent
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