New insights into bacterial CRISPR-Cas immunity

Scientists from Russia and USA led by Director of Skoltech Center for Data Intensive Medicine and Biotechnology, Professor Konstantin Severinov, have recently published two papers on the function of CRISPR-Cas – bacterial immune systems that revolutionized the field of genomic engineering. They have revealed unexpected ways by which CRISPR-Cas affects the interaction between bacteria and their viruses and identified molecular details of how immunological “memories” of viral infections are acquired by bacteria.

Prokaryotic CRISPR-Cas systems protect bacteria from mobile genetic elements such as viruses. In a bacterial chromosome a CRISPR-Cas system comprises a segment of DNA called “CRISPR array”, which contains short repeated sequences separated by unique spacers derived from foreign DNA, and Cas genes, encoding Cas proteins.  If a CRISPR spacer sequence matches a segment of foreign DNA that appears in the cell, Cas proteins can recognize and destroy it. A paper by Skoltech graduate student Alexandra Strotskaya and colleagues is devoted to analysis of infection by different bacteriophages (bacterial viruses) of bacteria with matching CRISPR spacers. “The most important and quite unexpected conclusion from our work is that unlike immune systems that people are accustomed to think about, a CRISPR-Cas system does not really save individual infected cells: all infected cell die, but, in contrast to infection of cells without CRISPR-Cas, there is no viral progeny produced. Thus, an infected cell that is able to recognize phage DNA with its CRISPR-Cas system commits an act of altruistic death, saving other cells in the population by decreasing the chances of re-infection” – says Alexandra.

The second paper, by Skoltech graduate student Olga Musharova, investigates how spacers matching mobile DNA find their way into CRISPR array as spacers. To recognize foreign DNA cells must have a matching spacer in their CRISPR array. Where and how do they get it from? Olga and her colleagues have found that acquisition of spacers into array occurs as the cell tries to fight the infection by degrading foreign DNA. Some of these attempts lead to generation of “spacer-sized” fragments of viral DNA that find their way into CRISPR array and then allow the cell to mount a protective CRISPR-Cas response. “Our results allowed us to build a model of the entire pathway. Some aspects of our model do not fit with those proposed by our colleagues from the US and Netherlands. We will have to work out the details and reconcile the differences in person during the upcoming international CRISPR meeting in Montana this summer”, says Olga.

The results of those studies were published in the Nucleic Acids Research journal.

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The Skolkovo Institute of Science and Technology (Skoltech) is a private graduate research university. Established in 2011 in collaboration with the Massachusetts Institute of Technology (MIT), Skoltech educates global leaders in innovation, advance scientific knowledge, and fosters new technologies to address critical issues facing Russia and the world. Skoltech conducts it work integrating the best practices of the best Russian and international educational and scientific research universities. Moreover, the university pays particular attention to entrepreneurship and innovative education. Website: https://www.skoltech.ru/

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