High genetic diversity is a hallmark of the gastric pathogen Helicobacter pylori. We used 454 sequencing technology to perform whole-genome comparisons for five sets of H. pylori strains that had been sequentially cultured from four chronically infected Colombians (isolation intervals = 3-16 y) and one human volunteer experimentally infected with H. pylori as part of a vaccine trial. The four sets of genomes from Colombian H. pylori differed by 27-232 isolated SNPs and 16-441 imported clusters of polymorphisms resulting from recombination. Imports (mean length = 394 bp) were distributed nonrandomly over the chromosome and frequently occurred in groups, suggesting that H. pylori first takes up long DNA fragments, which subsequently become partially integrated in multiple shorter pieces. Imports were present at significantly increased frequency in members of the hop family of outer membrane gene paralogues, some of which are involved in bacterial adhesion, suggesting diversifying selection. No evidence of recombination and few other differences were identified in the strain pair from an infected volunteer, indicating that the H. pylori genome is stable in the absence of mixed infection. Among these few differences was an OFF/ON switch in the phase-variable adhesin gene hopZ, suggesting strong in vivo selection for this putative adhesin during early colonization.comparative genomics | mutation M ore than one half of the human population is infected with Helicobacter pylori. Infection with this pathogen causes chronic gastritis, which can give rise to sequelae including peptic ulcers of stomach and duodenum, gastric atrophy, adenocarcinoma, and mucosa associated lymphoid tissue (MALT) lymphoma (1). Extensive allelic diversity and genetic variability are hallmarks of this species. They result from the combination of a high mutation rate (2) and frequent exchange of genetic material during mixed infections of one stomach with multiple H. pylori strains (3-7).We have previously analyzed the genetic relationships between strains of H. pylori that had been sequentially isolated from the same patient at time intervals ranging from 3 mo to 10 y (8) using multilocus sequence analysis of 10 (4) and 78 (8) loci, mostly from housekeeping genes. Bayesian inference was used to estimate recombination and mutation rates and the length of DNA fragments exchanged through recombination (imports). However, this multilocus approach did not allow conclusions about the chromosomal distribution of import events or about the relative frequencies of imports in different categories of genes.Here, we have used 454 pyrosequencing technology (9) to analyze the genomes of five sets of sequential isolates of H. pylori. In addition to four pairs of isolates from the earlier studies (with isolation intervals of 3 y), we also included recent follow-up isolates for two of the pairs that were obtained 16 y after the first isolates. Furthermore, we studied one pair of strains from a recent clinical trial where human volunteers were infected with H. pyl...
SummaryThe flagellar system of Helicobacter pylori , which comprises more than 40 mostly unclustered genes, is essential for colonization of the human stomach mucosa. In order to elucidate the complex transcriptional circuitry of flagellar biosynthesis in H. pylori and its link to other cell functions, mutants in regulatory genes governing flagellar biosynthesis ( rpoN , flgR , flhA , flhF , HP0244) and whole-genome microarray technology were used in this study. The regulon controlled by RpoN, its activator FlgR (FleR) and the cognate histidine kinase HP0244 (FleS) was characterized on a genome-wide scale for the first time.
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