Resistance mutation supply modulates the benefit of CRISPR immunity against virulent phages in Pseudomonas aeruginosa
4 affiliations
- 1Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
- 2Environment and Sustainability Institute, Centre for Ecology and Conservation, University of Exeter, Penryn, Cornwall, United Kingdom
- 3Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, United Kingdom
- 4Department of Microbiology, University of Helsinki, Helsinki, Finland
Abstract
Only a fraction of bacterial genomes encode CRISPR-Cas systems, but the selective causes of this variation are unexplained. How naturally virulent bacteriophages (phages) select for CRISPR immunity has rarely been tested experimentally. Here, we show against a panel of genetically and functionally diverse virulent phages that CRISPR immunity was not universally beneficial to Pseudomonas aeruginosa, and its fitness effect varied strongly between phages in predictable ways. In addition to mechanisms known to alter the effectiveness of CRISPR immunity, such as encoding a matching spacer or a protective nuclear shell, we show that the fitness effect of CRISPR immunity negatively associated with the probability of evolving receptor-based resistance to the phage via spontaneous mutation. The supply of resistance mutations differed strongly between very closely related lipopolysaccharide-binding phages and was associated with variation at the C-terminus of the tail fibre protein altering residues involved in hydrogen bonding and the predicted binding site. Our results show that CRISPR immunity is more beneficial against virulent phages that are harder to evolve resistance to via receptor mutations, suggesting that virulent phage community composition and diversity will be important drivers of the prevalence of CRISPR immunity.
Why do so few bacterial genomes encode CRISPR-Cas systems? This study of the fitness effect of CRISPR immunity against a diverse panel of phages in Pseudomonas aeruginosa reveals that a lower supply of receptor-based resistance mutations increases the benefits of CRISPR immunity.
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BibTeX
@article{wright2026resistance,
title = {{Resistance mutation supply modulates the benefit of CRISPR immunity against virulent phages in Pseudomonas aeruginosa}},
author = {Rosanna C. T. Wright and Simon C. Lovell and Anna Richmond and Christian Harrison and Eleri Ashworth and Aras Kadioglu and Joanne L. Fothergill and Ville-Petri Friman and Edze R. Westra and Michael A. Brockhurst},
journal = {PLOS Biology},
year = {2026},
month = nov,
doi = {10.1371/journal.pbio.3004094},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004094},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Resistance mutation supply modulates the benefit of CRISPR immunity against virulent phages in Pseudomonas aeruginosa
AU - Rosanna C. T. Wright
AU - Simon C. Lovell
AU - Anna Richmond
AU - Christian Harrison
AU - Eleri Ashworth
AU - Aras Kadioglu
AU - Joanne L. Fothergill
AU - Ville-Petri Friman
AU - Edze R. Westra
AU - Michael A. Brockhurst
PY - 2026
DA - 2026/11/02
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004094
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004094
AB - Only a fraction of bacterial genomes encode CRISPR-Cas systems, but the selective causes of this variation are unexplained. How naturally virulent bacteriophages (phages) select for CRISPR immunity has rarely been tested experimentally. Here, we show against a panel of genetically and functionally diverse virulent phages that CRISPR immunity was not universally beneficial to Pseudomonas aeruginosa, and its fitness effect varied strongly between phages in predictable ways. In addition to mechanisms known to alter the effectiveness of CRISPR immunity, such as encoding a matching spacer or a protective nuclear shell, we show that the fitness effect of CRISPR immunity negatively associated with the probability of evolving receptor-based resistance to the phage via spontaneous mutation. The supply of resistance mutations differed strongly between very closely related lipopolysaccharide-binding phages and was associated with variation at the C-terminus of the tail fibre protein altering residues involved in hydrogen bonding and the predicted binding site. Our results show that CRISPR immunity is more beneficial against virulent phages that are harder to evolve resistance to via receptor mutations, suggesting that virulent phage community composition and diversity will be important drivers of the prevalence of CRISPR immunity. Why do so few bacterial genomes encode CRISPR-Cas systems? This study of the fitness effect of CRISPR immunity against a diverse panel of phages in Pseudomonas aeruginosa reveals that a lower supply of receptor-based resistance mutations increases the benefits of CRISPR immunity.
SN - 1545-7885
ER -