Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan-Dec;16(1):2379440.
doi: 10.1080/19490976.2024.2379440. Epub 2024 Aug 12.

Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project

Filipa F Vale  1   2 , Richard J Roberts  3 , Ichizo Kobayashi  4   5   6   7 , M Constanza Camargo  8 , Charles S Rabkin  8 ; HpGP Research Network
Collaborators, Affiliations

Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project

Filipa F Vale et al. Gut Microbes. 2024 Jan-Dec.

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.

Keywords: H. pylori; HpGP; genome rearrangement; mobile elements; phage cycle; prophage.

PubMed Disclaimer

Conflict of interest statement

RJR works for New England Biolabs, a company that sells research reagents, including restriction enzymes and DNA methyltransferases, to the scientific community. JPG has served as speaker, consultant, and advisory member for or has received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen. EB-M has served as a speaker and consultant for Janssen, Chiesi, Kern and Takeda, and RMF, JCM, and CF own patent WO/2018/169423 on microbiome markers for gastric cancer.

Figures

Figure 1.
Figure 1.
Global overview of H. pylori prophage abundance and population structure.
Figure 2.
Figure 2.
Population structure and phylogenetics of the complete H. pylori prophages.
Figure 3.
Figure 3.
Prophage inactivation by genome rearrangement in 298 complete genomes.
Figure 4.
Figure 4.
Proposed mechanism for lysis/lytic cycle regulation in H. pylori prophages.
See this image and copyright information in PMC

References

    1. Mégraud F, Lehours P, Vale FF.. The history of Helicobacter pylori: from phylogeography to paleomicrobiology. Clin Microbiol Infect. 2016;22(11):922–28. doi: 10.1016/j.cmi.2016.07.013. - DOI - PubMed
    1. Malfertheiner P, Camargo MC, El-Omar E, Liou J-M, Peek R, Schulz C, Smith SI, Suerbaum S. Helicobacter pylori infection. Nat Rev Dis Prim [Internet]. 2023;9(1):19. doi: 10.1038/s41572-023-00431-8. - DOI - PMC - PubMed
    1. Ailloud F, Estibariz I, Suerbaum S. Evolved to vary: genome and epigenome variation in the human pathogen Helicobacter pylori. FEMS Microbiol Rev. 2021;45(1). doi: 10.1093/femsre/fuaa042. - DOI - PubMed
    1. Falush D, Wirth T, Linz B, Pritchard JK, Stephens M, Kidd M, Blaser MJ, Graham DY, Vacher S, Perez-Perez GI, et al. Traces of human migrations in Helicobacter pylori populations. Science. 2003;299(5612):1582–1585. doi: 10.1126/science.1080857. - DOI - PubMed
    1. Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW, et al. An African origin for the intimate association between humans and Helicobacter pylori. Nature. 2007;445(7130):915–918. doi: 10.1038/nature05562. - DOI - PMC - PubMed