Diverse defense systems and prophages in human-associated Bifidobacterium species reveal coevolutionary “arms race” dynamics

Docherty, James A.D., Cook, Ryan, Kiu, Raymond, Dyball, Xena, Brown, Teagan L., Kujawska, Magdalena, Smith, Rhianna lily, Phillips, Sarah, Watt, Rachel, Telatin, Andrea, Tiwari, Sumeet K., Hall, Lindsay J. and Adriaenssens, Evelien M. (2025) Diverse defense systems and prophages in human-associated Bifidobacterium species reveal coevolutionary “arms race” dynamics. Cell Reports, 44 (11). ISSN 2639-1856

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Abstract

Bacteria of the genus Bifidobacterium are pivotal for human health, especially in early life, where they dominate the gut microbiome in healthy infants. Bacteriophages, as drivers of gut bacterial composition, can affect bifidobacterial abundance. Here, we use a bioinformatics approach to explore direct interactions between human-associated Bifidobacterium spp. and prophages, as evidenced by their genomes. Analysis of 1,086 bifidobacterial genomes reveals the presence of complex systems that prevent viral invasion, with 34 defense systems and 56 subtypes detected, including several different CRISPR-Cas systems. CRISPR spacers target almost three-quarters of bifidobacteria-derived prophages, indicating dynamic interactions. At least one prophage is present in ∼67% of strains, with phages exhibiting high genomic diversity and evidence of historical recombination. These prophages encode various defense and anti-defense systems, such as anti-CRISPR genes and restriction-modification mechanisms. Overall, this investigation reveals that coevolutionary “arms race” dynamics drive genomic diversity in both bifidobacteria and their phages.

Item Type:	Article
Additional Information:	Data and code availability: • A full list of the 1,087 assembly accession numbers used in the final analysis of this study, including accompanying metadata, is available in Table S1 in the supplemental information. Please see BioProject accessions BioProject: PRJNA958097, PRJNA720750, PRJEB28188, and PRJNA1209344 for further information regarding genome assemblies. • All original and supporting code is publicly available at https://github.com/JDocherty67/Supporting_code_bif_defence_phages_coevolution (https://doi.org/10.5281/zenodo.17176911). • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
Uncontrolled Keywords:	anti-defense systems,bacteriophages,bifidobacterium,coevolutionary arms race,cp: microbiology,defense systems,human gut,human health,infant gut,infant health,prophages,biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	09 Apr 2026 14:30
Last Modified:	09 Apr 2026 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102737
DOI:	10.1016/j.celrep.2025.116542

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