TY - JOUR
T1 - Persistence of plasmids targeted by CRISPR interference in bacterial populations
AU - Mamontov, Viktor
AU - Martynov, Alexander
AU - Morozova, Natalia
AU - Bukatin, Anton
AU - Staroverov, Dmitry B.
AU - Lukyanov, Konstantin A.
AU - Ispolatov, Yaroslav
AU - Semenova, Ekaterina
AU - Severinov, Konstantin
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank A. Strotskaya for providing plasmids. This study was supported by NIH Grant GM10407 to K.S. Y.I. is supported by Fondo Nacional de Desarrollo Científico y Tecnológico Project 1200708. Experiments were partially carried out using the equipment provided by the Institute of Bioorganic Chemistry Core Facility (CKP IBCH; supported by Ministry of Science and Higher Education of the Russian Federation grant RFMEFI62117X0018). V.M. was supported by a grant from the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-10-2021-114).
Publisher Copyright:
© 2022 the Author(s).
PY - 2022/4/12
Y1 - 2022/4/12
N2 - CRISPR-Cas systems provide prokaryotes with an RNA-guided defense against foreign mobile genetic elements (MGEs) such as plasmids and viruses. A common mechanism by which MGEs avoid interference by CRISPR consists of acquisition of escape mutations in regions targeted by CRISPR. Here, using microbiological, live microscopy and microfluidics analyses we demonstrate that plasmids can persist for multiple generations in some Escherichia coli cell lineages at conditions of continuous targeting by the type I-E CRISPR-Cas system. We used mathematical modeling to show how plasmid persistence in a subpopulation of cells mounting CRISPR interference is achieved due to the stochastic nature of CRISPR interference and plasmid replication events. We hypothesize that the observed complex dynamics provides bacterial populations with long-term benefits due to continuous maintenance of mobile genetic elements in some cells, which leads to diversification of phenotypes in the entire community and allows rapid changes in the population structure to meet the demands of a changing environment.
AB - CRISPR-Cas systems provide prokaryotes with an RNA-guided defense against foreign mobile genetic elements (MGEs) such as plasmids and viruses. A common mechanism by which MGEs avoid interference by CRISPR consists of acquisition of escape mutations in regions targeted by CRISPR. Here, using microbiological, live microscopy and microfluidics analyses we demonstrate that plasmids can persist for multiple generations in some Escherichia coli cell lineages at conditions of continuous targeting by the type I-E CRISPR-Cas system. We used mathematical modeling to show how plasmid persistence in a subpopulation of cells mounting CRISPR interference is achieved due to the stochastic nature of CRISPR interference and plasmid replication events. We hypothesize that the observed complex dynamics provides bacterial populations with long-term benefits due to continuous maintenance of mobile genetic elements in some cells, which leads to diversification of phenotypes in the entire community and allows rapid changes in the population structure to meet the demands of a changing environment.
KW - CRISPR interference
KW - CRISPR-Cas
KW - mobile genetic elements
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U2 - 10.1073/pnas.2114905119
DO - 10.1073/pnas.2114905119
M3 - Article
C2 - 35394860
AN - SCOPUS:85127886484
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
M1 - 2114905119
ER -