Type III-A CRISPR immunity promotes mutagenesis of staphylococci

• Published in: Nature (London) Vol. 592; no. 7855; pp. 611 - 615
• Main Authors: Mo, Charlie Y., Mathai, Jacob, Rostøl, Jakob T., Varble, Andrew, Banh, Dalton V., Marraffini, Luciano A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2021; Nature Publishing Group
• Subjects: 45/23; 45/29; 45/70; 45/77; 631/326/1321; 631/326/22; 631/326/41/2531; Analysis; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Bacteria; Bacteriophages - classification; Bacteriophages - physiology; Biological evolution; Cell division; CRISPR; CRISPR-Associated Proteins - metabolism; CRISPR-Cas Systems - genetics; CRISPR-Cas Systems - immunology; Deoxyribonuclease; Deoxyribonucleases - metabolism; DNA; DNA binding proteins; DNA damage; DNA, Single-Stranded - genetics; DNA, Single-Stranded - metabolism; Drug resistance in microorganisms; Drug Resistance, Microbial - drug effects; Evolution; Experiments; Gene transfer; Genes; Genetic aspects; Genetic diversity; Genomes; Genomics; Horizontal transfer; Humanities and Social Sciences; Identification and classification; Immunity (Disease); Microorganisms; multidisciplinary; Mupirocin; Mutagenesis; Mutation; Nuclease; Nucleases; Nucleotide sequence; Plasmids; RNA; RNA polymerase; Science; Science (multidisciplinary); SOS response; SOS Response, Genetics - drug effects; Staphylococcus; Staphylococcus - drug effects; Staphylococcus - genetics; Staphylococcus - immunology; Staphylococcus - virology; Staphylococcus aureus - drug effects; Staphylococcus aureus - genetics; Staphylococcus aureus - virology; Staphylococcus epidermidis - drug effects; Staphylococcus epidermidis - genetics; Staphylococcus epidermidis - virology; Staphylococcus infections; Time Factors; Transposons; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-021-03440-3

Horizontal gene transfer and mutation are the two major drivers of microbial evolution that enable bacteria to adapt to fluctuating environmental stressors 1 . Clustered, regularly interspaced, short palindromic repeats (CRISPR) systems use RNA-guided nucleases to direct sequence-specific destruction of the genomes of mobile genetic elements that mediate horizontal gene transfer, such as conjugative plasmids 2 and bacteriophages 3 , thus limiting the extent to which bacteria can evolve by this mechanism. A subset of CRISPR systems also exhibit non-specific degradation of DNA 4 , 5 ; however, whether and how this feature affects the host has not yet been examined. Here we show that the non-specific DNase activity of the staphylococcal type III-A CRISPR–Cas system increases mutations in the host and accelerates the generation of antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis . These mutations require the induction of the SOS response to DNA damage and display a distinct pattern. Our results demonstrate that by differentially affecting both mechanisms that generate genetic diversity, type III-A CRISPR systems can modulate the evolution of the bacterial host. In Staphylococcus epidermidis and Staphylococcus aureus , non-specific DNase activity of the type III-A CRISPR–Cas system increases the rate of mutations in the host and accelerates the evolution of resistance to antibiotics and to phage.