Gene Content, Phage Cycle Regulation Model and Prophage Inactivation Disclosed by Prophage Genomics in the Helicobacter pylori Genome Project

Authors

Filipa F Vale
Richard J Roberts
Ichizo Kobayashi
M Constanza Camargo
Charles S Rabkin
HpGP Research Network

Publication Date

1-1-2024

Journal

Gut Microbes

DOI

10.1080/19490976.2024.2379440

PMID

39132840

PMCID

PMC11321410

PubMedCentral® Posted Date

8-12-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Helicobacter pylori, Prophages, Genome, Bacterial, Humans, Phylogeny, Genomics, Helicobacter Infections, HpGP, H. pylori, prophage, mobile elements, genome rearrangement, phage cycle

Abstract

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified genome rearrangements and assessed the impact of prophage presence on bacterial gene disruption and methylome. We found that 29.5% (298) of the HpGP genomes contain prophages, of which only 32.2% (96) were complete, minimizing the burden of prophage carriage. The prevalence of H. pylori prophage sequences was variable by geography and ancestry, but not by disease status of the human host. Prophage insertion occasionally results in gene disruption that can change the global bacterial epigenome. Gene function prediction allowed the development of the first model for lysogenic-lytic cycle regulation in H. pylori. We have disclosed new prophage inactivation mechanisms that appear to occur by genome rearrangement, merger with other mobile elements, and pseudogene accumulation. Our analysis provides a comprehensive framework for H. pylori prophage biological and genomics, offering insights into lysogeny regulation and bacterial adaptation to prophages.