CRISPR provides acquired resistance against viruses in prokaryotes

CRISPR provides acquired resistance against viruses in prokaryotes

| Rodolphe Barrangou¹, Christophe Fremaux², Hélène Deveau³, Melissa Richards¹, Patrick Boyaval², Sylvain Moineau³, Dennis A. Romero¹, Philippe Horvath²*
CRISPR is a key feature in the genomes of most bacteria and archaea, involved in resistance to bacteriophages. When bacteria are infected by phages, they integrate new spacers from phage genomes, which determine resistance through sequence similarity. Bacteriophages are abundant and impact microbial ecology and evolution, leading to the development of defense mechanisms by bacteria. CRISPR, along with associated cas genes, provides resistance by matching spacer sequences to phage sequences. In *Streptococcus thermophilus*, CRISPR loci contain spacers that correlate with phage resistance. Analysis of phage-resistant mutants showed that additional spacers in CRISPR1 were derived from phage DNA, and that spacer content influenced resistance. Experiments demonstrated that adding specific spacers could confer resistance, while their absence or mutations reduced it. Inactivation of cas genes, such as cas5, reduced phage resistance, suggesting their role in CRISPR-mediated immunity. CRISPR spacers are inherited and can be used for evolutionary and genomic studies. The CRISPR/Cas system provides a nucleic-acid based immunity system, distinct from eukaryotic amino-acid based immunity. It plays a significant role in prokaryotic evolution and ecology, offering insights into phage exposure and predicting phage sensitivity. The system may also be used for virus defense and controlling mobile genetic elements. CRISPR loci are widespread in bacteria and archaea, providing new insights into their co-evolution with phages.CRISPR is a key feature in the genomes of most bacteria and archaea, involved in resistance to bacteriophages. When bacteria are infected by phages, they integrate new spacers from phage genomes, which determine resistance through sequence similarity. Bacteriophages are abundant and impact microbial ecology and evolution, leading to the development of defense mechanisms by bacteria. CRISPR, along with associated cas genes, provides resistance by matching spacer sequences to phage sequences. In *Streptococcus thermophilus*, CRISPR loci contain spacers that correlate with phage resistance. Analysis of phage-resistant mutants showed that additional spacers in CRISPR1 were derived from phage DNA, and that spacer content influenced resistance. Experiments demonstrated that adding specific spacers could confer resistance, while their absence or mutations reduced it. Inactivation of cas genes, such as cas5, reduced phage resistance, suggesting their role in CRISPR-mediated immunity. CRISPR spacers are inherited and can be used for evolutionary and genomic studies. The CRISPR/Cas system provides a nucleic-acid based immunity system, distinct from eukaryotic amino-acid based immunity. It plays a significant role in prokaryotic evolution and ecology, offering insights into phage exposure and predicting phage sensitivity. The system may also be used for virus defense and controlling mobile genetic elements. CRISPR loci are widespread in bacteria and archaea, providing new insights into their co-evolution with phages.
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