Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages
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Date
2025-05-23
Authors
Cortés-Martín, Adrián
Buttimer, Colin
Maier, Jessie L.
Tobin, Ciara A.
Draper, Lorraine A.
Ross, R. Paul
Kleiner, Manuel
Hill, Colin
Shkoporov, Andrey N.
Journal Title
Journal ISSN
Volume Title
Publisher
Taylor & Francis
Published Version
Abstract
Bacteriophages (phages) and bacteria within the gut microbiome persist in long-term stablecoexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employa variety of mechanisms to evade phage infection, while phages rely on counterstrategies toovercome these defenses. Among the most abundant phages in the gut are the crAss-like phagesthat infect members of the order Bacteroidales, in particular, genus Bacteroides. In this study, weexplored some of the mechanisms enabling the co-existence of four phage-Bacteroidales hostpairs in vitro using a multi-omics approach (transcriptomics, proteomics and metabolomics). Theseincluded three Bacteroides species paired with three crAss-like phages (Bacteroides intestinalis andфcrAss001, Bacteroides xylanisolvens and фcrAss002, and an acapsular mutant of Bacteroidesthetaiotaomicron with DAC15), and Parabacteroides distasonis paired with the siphovirus фPDS1.We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechan-ism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternativeresistance mechanisms, while potentially less efficient than CPS phase variation, can be activatedto support bacterial survival by regulating gene expression and resulting in metabolic adaptations,particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phasevariation, enable bacterial populations to persist in the presence of phages, and vice versa. Anacapsular variant of B. thetaiotaomicron demonstrated broader transcriptomic, proteomic, andmetabolomic changes, supporting the involvement of additional resistance mechanisms beyondCPS variation. This study advances our understanding of long-term phage–host interaction, offer-ing insights into the long-term persistence of crAss-like phages and extending these observationsto other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions isessential for designing effective phage therapies and improving human health through targetedmicrobiome interventions.
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Keywords
Bacteriophages , Gut microbiome , Intestinal microbiota , Phage-bacteriainteraction , Virome , Crassphages , Bacteroides , Parabacteroides , Crassvirales , Co-culture
Citation
Cortés-Martín, A., Buttimer, C., Maier, J. L., Tobin, C. A., Draper, L. A., Ross, R. P., Kleiner, M., Hill, C. and Shkoporov, A. N. (2025) ‘Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages’, Gut Microbes, 17(1), 2507775 (23pp). https://doi.org/10.1080/19490976.2025.2507775