Abstract
Phages impose strong selection on bacteria to evolve resistance against viral predation. Bacteria can rapidly evolve phage resistance via receptor mutation or using their CRISPR-Cas adaptive immune systems. Acquisition of CRISPR immunity relies on the insertion of a phage-derived sequence into CRISPR arrays in the bacterial genome. Using Pseudomonas aeruginosa and its phage DMS3vir as a model, we demonstrate that conditions that reduce bacterial growth rates, such as exposure to bacteriostatic antibiotics (which inhibit cell growth without killing), promote the evolution of CRISPR immunity. We demonstrate that this is due to slower phage development under these conditions, which provides more time for cells to acquire phage-derived sequences and mount an immune response. Our data reveal that the speed of phage development is a key determinant of the evolution of CRISPR immunity and suggest that use of bacteriostatic antibiotics can trigger elevated levels of CRISPR immunity in human-associated and natural environments.
| Original language | English |
|---|---|
| Pages (from-to) | 31-40.e5 |
| Number of pages | 16 |
| Journal | Cell Host & Microbe |
| Volume | 30 |
| Issue number | 1 |
| Early online date | 20 Dec 2021 |
| DOIs | |
| Publication status | Published - 12 Jan 2022 |
Bibliographical note
Funding Information:This work was funded by grants from the European Research Council under the European Union's Horizon 2020 research and innovation programme (ERC-2017-ADG-788405 to M.D.S. and ERC-STG-2016-714478 to E.R.W.). E.R.W. was further supported by NERC Independent Research Fellowship (NE/M018350/1). Work in K.S. lab was supported by the Ministry of Science and Higher Education of the Russian Federation under (grant 075-15-2019-1661), NIH National Institute of Health (grant RO1 10407), and the Russian Science Foundation (grant 19-74-20130). Conceptualization of the study was done by T.D. and E.R.W. Experimental design was carried out by T.D. and E.R.W. Bacterial evolution, competition, and growth experiments, as well as phage infection assays were done by T.D. with assistance from E.K. and MIC measurements were done by E.K. Microfluidics experiments were designed and carried out by U.L. and S.P. Formal analysis of results was done by T.D. K.S. and M.D.S. contributed to discussions and provided feedback throughout the project. T.D. wrote the original draft of the manuscript, with later edits and reviews by T.D. K.S. S.P. M.D.S. and E.R.W. The authors declare no competing interests.
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