期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：14
页码：7550-7552
DOI：10.1073/pnas.2002746117
出版社：The National Academy of Sciences of the United States of America
摘要：In 2007, researchers at Danisco interested in fortifying the lactic acid bacteria used to produce dairy products such as milk and cheese against attack by phage showed that CRISPR provided resistance (1). These phage infections were common in industrial dairy fermentation, and it was hugely significant that insertion of multiple spacers in the bacterial CRISPR system was shown to protect against them. Intriguingly, rare mutations in the phage regions from which these spacers were derived were also shown to give rise to lineages that could again reinfect the bacteria. Thus was born the study of the phage–bacteria immune system arms race. In PNAS, Bradde et al. (2) present a theory of the tradeoff between broad coverage of phage types and efficient use of a limited number of enzymes in each bacterium that leads to an optimal size of the CRISPR immune system. Earlier bioinformatics studies had shown that the majority of spacers in bacterial CRISPR arrays matched phage or conjugative plasmids that naturally infect the bacteria containing the CRISPR array (3). These CRISPR spacers were found to be the most polymorphic sites in plague Yersinia pestis strains, and thus potentially useful for forensically tracing the origins of prokaryotic pathogens (4). In the same year, bioinformatic analysis showed that spacers from multiple strains and species of Streptococcus were homologous to phage and plasmid sequences (5). The sensitivity of Streptococcus thermophilus to phage was shown to correlate with the number of spacers in the CRISPR locus. A significant number of studies followed up on these observations that bacterial resistance to phage correlated with spacer diversity in the CRISPR array (6⇓–8). Later studies confirmed the ability of S. thermophilus to insert phage sequences into its CRISPR array and analyzed thousands of spacers from over a hundred strains (9). The … [↵][1]1Email: mwdeem{at}rice.edu. [1]: #xref-corresp-1-1
