Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species
Author(s)
Mannion, Anthony; Shen, Zeli; Fox, James G
Download12864_2018_Article_5171.pdf (4.352Mb)
PUBLISHER_CC
Publisher with Creative Commons License
Creative Commons Attribution
Terms of use
Metadata
Show full item recordAbstract
Background
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. 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.
Results
Whole-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.
Conclusions
The 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.
Date issued
2018-11Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative MedicineJournal
BMC Genomics
Publisher
Biomed Central Ltd
Citation
Mannion, Anthony et al. "Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species." BMC Genomics 19 (November 2018): 830 © 2018 The Author(s)
Version: Final published version
ISSN
1471-2164