Insertion sequence transposition inactivates CRISPR-Cas immunity

Yong Sheng, Hengyu Wang, Yixin Ou, Yingying Wu, Wei Ding, Meifeng Tao, Shuangjun Lin, Zixin Deng (), Linquan Bai () and Qianjin Kang ()
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Yong Sheng: Shanghai Jiao Tong University
Hengyu Wang: Shanghai Jiao Tong University
Yixin Ou: Shanghai Jiao Tong University
Yingying Wu: Shanghai Jiao Tong University
Wei Ding: Shanghai Jiao Tong University
Meifeng Tao: Shanghai Jiao Tong University
Shuangjun Lin: Shanghai Jiao Tong University
Zixin Deng: Shanghai Jiao Tong University
Linquan Bai: Shanghai Jiao Tong University
Qianjin Kang: Shanghai Jiao Tong University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, we screened prokaryotic genomic sequences and identified multiple natural transpositions of insertion sequences (ISs) into cas genes, thus inactivating CRISPR-Cas defenses. We then generated an IS-trapping system, using Escherichia coli strains with various ISs and an inducible cas nuclease, to monitor IS insertions into cas genes following the induction of double-strand DNA breakage as a physiological host stress. We identified multiple events mediated by different ISs, especially IS1 and IS10, displaying substantial relaxed target specificity. IS transposition into cas was maintained in the presence of DNA repair machinery, and transposition into other host defense systems was also detected. Our findings highlight the potential of ISs to counter CRISPR activity, thus increasing bacterial susceptibility to foreign DNA invasion.

Date: 2023
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DOI: 10.1038/s41467-023-39964-7

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