Abstract
BackgroundThe genus Helicobacter are gram-negative, microaerobic, flagellated, mucus-inhabiting bacteria associated with gastrointestinal inflammation and classified as gastric or enterohepatic Helicobacter species (EHS) according to host species and colonization niche. While there are over 30 official species, little is known about the physiology and pathogenic mechanisms of EHS, which account for most in the genus, as well as what genetic factors differentiate gastric versus EHS, given they inhabit different hosts and colonization niches. The objective of this study was to perform a whole-genus comparative analysis of over 100 gastric versus EHS genomes in order to identify genetic determinants that distinguish these Helicobacter species and provide insights about their evolution/adaptation to different hosts, colonization niches, and mechanisms of virulence.ResultsWhole-genome phylogeny organized Helicobacter species according to their presumed gastric or EHS classification. Analysis of orthologs revealed substantial heterogeneity in physiological and virulence-related genes between gastric and EHS genomes. Metabolic reconstruction predicted that unlike gastric species, EHS appear asaccharolytic and dependent on amino/organic acids to fuel metabolism. Additionally, gastric species lack de novo biosynthetic pathways for several amino acids and purines found in EHS and instead rely on environmental uptake/salvage pathways. Comparison of virulence factor genes between gastric and EHS genomes identified overlapping yet distinct profiles and included canonical cytotoxins, outer membrane proteins, secretion systems, and survival factors.ConclusionsThe major differences in predicted metabolic function suggest gastric species and EHS may have evolved for survival in the nutrient-rich stomach versus the nutrient-devoid environments, respectively. Contrasting virulence factor gene profiles indicate gastric species and EHS may utilize different pathogenic mechanisms to chronically infect hosts and cause inflammation and tissue damage. The findings from this study provide new insights into the genetic differences underlying gastric versus EHS and support the need for future experimental studies to characterize these pathogens.
Highlights
The genus Helicobacter are gram-negative, microaerobic, flagellated, mucus-inhabiting bacteria associated with gastrointestinal inflammation and classified as gastric or enterohepatic Helicobacter species (EHS) according to host species and colonization niche
Phylogenetic classification of gastric and enterohepatic Helicobacter species Phylogenetic trees based on 16s rRNA genes sequences, pan-genome orthologous gene clusters, and average nucleotide identity (ANI) similarity were constructed for taxonomic organization of gastric and EHS
It has been noted that phylogenetic organization of Helicobacter spp. based on 16s rRNA gene sequences is discordant with phylogenies based on other genes, isolation/colonization site, biochemical traits, or morphological characteristics [11]
Summary
The genus Helicobacter are gram-negative, microaerobic, flagellated, mucus-inhabiting bacteria associated with gastrointestinal inflammation and classified as gastric or enterohepatic Helicobacter species (EHS) according to host species and colonization niche. Since Helicobacter pylori was discovered in 1982 as the cause of chronic gastritis and later established its role in peptic ulcers and stomach cancers [1, 2], the genus Helicobacter has expanded to include multiple enterohepatic Helicobacter species (EHS) that colonize and can induce inflammation and cancer in the lower bowel, liver, and gallbladder in susceptible hosts [3,4,5]. The genus includes over 30 formally named species These gram-negative, spiral-shaped bacterial species have been detected and isolated from the stomach, gastrointestinal tract, liver, and gallbladder in mammals, birds, and reptiles. Most research has focused on H. pylori and related gastric species that have been isolated and cause disease in humans, leaving a void in our understanding of the mechanisms of colonization and virulence potential in EHS
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