A comprehensive analysis of Helicobacter pylori plasticity zones reveals that they are integrating conjugative elements with intermediate integration specificity

Abstract

BackgroundThe human gastric pathogen Helicobacter pylori is a paradigm for chronic bacterial infections. Its persistence in the stomach mucosa is facilitated by several mechanisms of immune evasion and immune modulation, but also by an unusual genetic variability which might account for the capability to adapt to changing environmental conditions during long-term colonization. This variability is reflected by the fact that almost each infected individual is colonized by a genetically unique strain. Strain-specific genes are dispersed throughout the genome, but clusters of genes organized as genomic islands may also collectively be present or absent.ResultsWe have comparatively analysed such clusters, which are commonly termed plasticity zones, in a high number of H. pylori strains of varying geographical origin. We show that these regions contain fixed gene sets, rather than being true regions of genome plasticity, but two different types and several subtypes with partly diverging gene content can be distinguished. Their genetic diversity is incongruent with variations in the rest of the genome, suggesting that they are subject to horizontal gene transfer within H. pylori populations. We identified 40 distinct integration sites in 45 genome sequences, with a conserved heptanucleotide motif that seems to be the minimal requirement for integration.ConclusionsThe significant number of possible integration sites, together with the requirement for a short conserved integration motif and the high level of gene conservation, indicates that these elements are best described as integrating conjugative elements (ICEs) with an intermediate integration site specificity.

Comparative Genomics ofH. pyloriand Non-PyloriHelicobacterSpecies to Identify New Regions Associated with Its Pathogenicity and Adaptability

“…Previous studies indicated that H. pylori has a high rate of gene recombination and unusual genetic flexibility, and those traits were considered to be helpful for the adaption to the dynamic environment [18, 19]. Even though massive virulence factors of them have been studied, the mechanisms that the essential genome components of H. pylori lead to its large scale epidemic and gastrointestinal environment adaptation within human beings remain to be further elucidated.…”

The expression of Helicobacter pylori tfs plasticity zone cluster is regulated by pH and adherence, and its composition is associated with differential gastric IL‐8 secretion

“…24 More, we found genetic segments usually associated with a tfs4c cluster in other strains belonging to hpEurope and hspWAfrica1 24 More, we found genetic segments usually associated with a tfs4c cluster in other strains belonging to hpEurope and hspWAfrica1…”

“…[15][16][17][18] Another virulence factor, dupA, has been controversially associated with duodenal ulcer development. 24 These clusters are characterized according to their gene composition and genetic sequence variation. It is believed that this cluster codes for an alternative type IV secretion system, being dupA the homolog to virB4.…”

“…24 The subcluster types belonging to tfs4 are more genetically diverse, being majorly defined according to differences on their genetic composition at the ends of the cluster (tfs4b) or at the central region (tfs4c). 24 The subcluster types belonging to tfs4 are more genetically diverse, being majorly defined according to differences on their genetic composition at the ends of the cluster (tfs4b) or at the central region (tfs4c).…”

“…24 Despite the presence of these diverse secretion systems in the plasticity zone, their impact in the virulence of H. pylori strains remains elusive. 24 Despite the presence of these diverse secretion systems in the plasticity zone, their impact in the virulence of H. pylori strains remains elusive.…”