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Updated: Jul 5, 2025
Substrate Generation for Endonucleases of CRISPR/Cas Systems
Published on: September 8, 2012
My host's enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages
Berit Siedentop1, Dario Rüegg1, Sebastian Bonhoeffer1
1Institute for Integrative Biology, ETH Zürich, Zürich, Switzerland.
Abstract:
Bacteria are infected by mobile genetic elements like plasmids and virulent phages, and those infections significantly impact bacterial ecology and evolution. Recent discoveries reveal that some plasmids carry anti-phage immune systems like CRISPR-Cas, suggesting that plasmids may participate in the coevolutionary arms race between virulent phages and bacteria. Intuitively, this seems reasonable as virulent phages kill the plasmid's obligate host. However, the efficiency of CRISPR-Cas systems carried by plasmids can be expected to be lower than those carried by the chromosome due to continuous segregation loss, creating susceptible cells for phage amplification. To evaluate the anti-phage protection efficiency of CRISPR-Cas on plasmids, we develop a stochastic model describing the dynamics of a virulent phage infection against which a conjugative plasmid defends using CRISPR-Cas. We show that CRISPR-Cas on plasmids provides robust protection, except in limited parameter sets. In these cases, high segregation loss favours phage outbreaks by generating a population of defenceless cells on which the phage can evolve and escape CRISPR-Cas immunity. We show that the phage's ability to exploit segregation loss depends strongly on the evolvability of both CRISPR-Cas and the phage itself.
Insights
Plasmids carrying CRISPR-Cas systems offer robust phage defense for bacteria. However, high plasmid loss can enable phage outbreaks by creating susceptible cells, impacting bacterial evolution.
Area of Science:
- Microbiology
- Evolutionary Biology
- Genetics
Background:
- Bacteria face infections from mobile genetic elements like plasmids and phages, influencing their ecology and evolution.
- Plasmids can harbor anti-phage systems, such as CRISPR-Cas, suggesting a role in bacterial-phage coevolutionary dynamics.
Purpose of the Study:
- To evaluate the anti-phage protection efficiency of CRISPR-Cas systems located on plasmids.
- To model the dynamics of virulent phage infection in the presence of plasmid-mediated CRISPR-Cas immunity.
Main Methods:
- Development of a stochastic model to simulate phage-bacteria interactions.
- Analysis of CRISPR-Cas mediated defense considering plasmid segregation loss.
- Investigation of phage evolution and escape mechanisms.
Main Results:
- Plasmid-borne CRISPR-Cas systems generally provide strong protection against virulent phages.
- High rates of plasmid segregation loss can compromise CRISPR-Cas effectiveness, leading to phage outbreaks.
- Phage evolution and escape are facilitated by susceptible cells arising from plasmid loss.
Conclusions:
- Plasmid-based CRISPR-Cas immunity is largely effective but vulnerable to high segregation loss.
- The interplay between plasmid loss, phage evolvability, and CRISPR-Cas evolution dictates protection efficacy.
- Understanding these dynamics is crucial for comprehending bacterial-phage coevolution.
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