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While it is well established that bacterial genomes encode multiple and diverse antiphage systems, the reasons for their co-occurrence and their heterogeneous distribution remain debated. This review examines why bacteria accumulate antiphage systems and how this influences phage-bacteria interactions, particularly in the context of phage therapy. Two main hypotheses may explain this phenomenon: (i) the pan-immunity hypothesis, which suggests that defence system accumulation provides protection against phage predation at the community level, and (ii) mobile genetic element (MGE) competition, where defence systems primarily protect intra-bacterial MGEs against other ones rather than the bacterial host itself. The ecological context also influences the distribution of antiphage systems, with defencee accumulation shaping phage-bacteria interactions in diverse communities but playing a lesser role at the species level, potentially explaining why multiple defences do not strongly limit phage host range in therapeutic settings. Finally, we address the challenges in understanding the drivers shaping the distribution of defence systems across bacterial genomes (expressions, costs, etc.) and their implications for elucidating the ecological role of defence systems and optimizing phage therapy strategies.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
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http://dx.doi.org/10.1098/rstb.2024.0082 | DOI Listing |
Nucleic Acids Res
September 2025
School of Microbiology, University College Cork, Cork, T12 Y337, Ireland.
The genomes of 43 distinct lactococcal strains were reconstructed by a combination of long- and short-read sequencing, resolving the plasmid complement and methylome of these strains. The genomes comprised 43 chromosomes of approximately 2.5 Mb each and 269 plasmids ranging from 2 to 211 kb (at an average occurrence of 6 per strain).
View Article and Find Full Text PDFNat Microbiol
September 2025
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Restriction-modification (R-M) systems protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage defences, R-M systems pose a major risk of autoimmunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. Pseudomonas aeruginosa strains experience the temporary inactivation of restriction endonucleases following growth at high temperatures, but the reason and mechanisms for this phenomenon are unknown.
View Article and Find Full Text PDFbioRxiv
August 2025
UC San Francisco, Dept. of Microbiology & Immunology, 600 16th St N374, San Francisco, CA 94158.
Anti-bacteriophage systems like restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable identification of invaders. How Gabija, a highly prevalent nuclease-helicase anti-phage system, executes self- vs. non-self-discrimination remains unknown.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
September 2025
Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
the causative agent of cholera, has triggered seven pandemics, with the seventh pandemic emerging in 1961. The success of seventh pandemic El Tor (7PET) as a human pathogen is linked to its acquisition of mobile genetic elements (MGEs) like the CTXΦ prophage and pathogenicity island 1 (VPI-1). Additional MGEs, including VPI-2 and the seventh pandemic islands (VSP-I and VSP-II), are thought to have further enhanced the pathogen's virulence potential.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
September 2025
Department of Genetics and Genomics, Pasteur Institute, 75015 Paris, France.
While it is well established that bacterial genomes encode multiple and diverse antiphage systems, the reasons for their co-occurrence and their heterogeneous distribution remain debated. This review examines why bacteria accumulate antiphage systems and how this influences phage-bacteria interactions, particularly in the context of phage therapy. Two main hypotheses may explain this phenomenon: (i) the pan-immunity hypothesis, which suggests that defence system accumulation provides protection against phage predation at the community level, and (ii) mobile genetic element (MGE) competition, where defence systems primarily protect intra-bacterial MGEs against other ones rather than the bacterial host itself.
View Article and Find Full Text PDF