In silico proteomic and phylogenetic analysis of the outer membrane protein repertoire of gastric Helicobacter species

Eva Bauwens,Freddy Haesebrouck,Richard Ducatelle,Han Remaut,Steffen Backert,James Fox,Annemieke Smet,Joemar Taganna,Fanny Peters,Alfred Tay,Myrthe Joosten,Mirko Rossi,Ayla Debraekeleer

doi:10.1038/s41598-018-32476-1

Abstract

Helicobacter (H.) pylori is an important risk factor for gastric malignancies worldwide. Its outer membrane proteome takes an important role in colonization of the human gastric mucosa. However, in zoonotic non-H. pylori helicobacters (NHPHs) also associated with human gastric disease, the composition of the outer membrane (OM) proteome and its relative contribution to disease remain largely unknown. By means of a comprehensive survey of the diversity and distribution of predicted outer membrane proteins (OMPs) identified in all known gastric Helicobacter species with fully annotated genome sequences, we found genus- and species-specific families known or thought to be implicated in virulence. Hop adhesins, part of the Helicobacter-specific family 13 (Hop, Hor and Hom) were restricted to the gastric species H. pylori, H. cetorum and H. acinonychis. Hof proteins (family 33) were putative adhesins with predicted Occ- or MOMP-family like 18-stranded β-barrels. They were found to be widespread amongst all gastric Helicobacter species only sporadically detected in enterohepatic Helicobacter species. These latter are other members within the genus Helicobacter, although ecologically and genetically distinct. LpxR, a lipopolysaccharide remodeling factor, was also detected in all gastric Helicobacter species but lacking as well from the enterohepatic species H. cinaedi, H. equorum and H. hepaticus. In conclusion, our systemic survey of Helicobacter OMPs points to species and infection-site specific members that are interesting candidates for future virulence and colonization studies.

Highlights

H. pylori colonizes the stomach of more than 50% of the human population
The mean number of outer membrane proteins (OMPs) was lower for the 4 enterohepatic helicobacters with a minimum of 24 OMPs for H. equorum eqF1 and a maximum of 55 OMPs for H. trogontum R3554), compared to the gastric Helicobacter species with a minimum of 47 OMPs for H. salomonis M45 and a maximum of 118 OMPs for H. cetorum MIT 00–7128)
We have analysed the genome sequences from a total of 54 different strains of the genera Helicobacter, Campylobacter and E. coli for their presence of OMPs

Summary

Introduction

H. pylori colonizes the stomach of more than 50% of the human population. Infection with this microbe is considered to be the most important risk factor for gastric malignancies worldwide[1,2]. Besides H. pylori, non-H. pylori Helicobacter (NHPH) species have been associated with gastric disease in humans, including gastritis, gastric and duodenal ulcers and mucosa-associated lymphoid tissue (MALT) lymphoma. Recent comparative genomic studies highlighted that gastric NHPHs lack all known H. pylori adhesins described so far[15,16,17,18] They share only few homologs of the Hor and Hom family. In the present study, we screened the genomes in silico from all gastric Helicobacter species known so far, for the presence of genes encoding putative OMPs. The predicted OMPs were classified into families based on their protein sequence homology, using 3 different protein databases. This study identified several unique OMP families that are possibly important for colonization and virulence, in gastric Helicobacter species

Methods

Results

Conclusion