Evolution of Helicobacter spp: variability of virulence factors and their relationship to pathogenicity.

Abstract

Virulence factors (VF) are bacteria-associated molecules that assist to colonize the host at the cellular level. Bacterial virulence is highly dynamic and specific pathogens have a broad array of VFs. The genus Helicobacter is gram-negative, microaerobic, flagellated, and mucus-inhabiting bacteria associated with gastrointestinal inflammation. To investigate about their pathogenicity, several Helicobacter species have been characterized and sequenced. Since the variability and possible origin of VF in the genus are not clear, our goal was to perform a comparative analysis of Helicobacter species in order to investigate VF variability and their evolutionary origin. The complete genomes of 22 Helicobacter species available in NCBI were analyzed, using computational tools. We identifyed gain and loss events in VF genes, which were categorized in seven functional groups to determine their most parsimonious evolutionary origin. After verifying the annotation of all VF genes, a phylogeny from conserved VF organized by Helicobacter species according to gastric Helicobacter species (GHS) or enterohepatic (EHS) classification was obtained. Gain and loss analysis of VF orthologous in Helicobacter ssp revealed the most possible evolutionary origin for each gene set. Microevolutionary events in urease and flagella genes were detected during the evolution of the genus. Our results pointed that acquisition of ureases and adherence genes and deletion of cytotoxins in some lineages, as well as variation in VF genes copy number, would be related to host adaptation during evolution of the Helicobacter genus. Our findings provided new insights about the genetic differences between GHS and EHS and their relationship with pathogenicity.