Title | Broad Targeting Specificity during Bacterial Type III CRISPR-Cas Immunity Constrains Viral Escape. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Pyenson NC, Gayvert K, Varble A, Elemento O, Marraffini LA |
Journal | Cell Host Microbe |
Volume | 22 |
Issue | 3 |
Pagination | 343-353.e3 |
Date Published | 2017 Sep 13 |
ISSN | 1934-6069 |
Keywords | Bacterial Proteins, Bacteriophages, CRISPR-Cas Systems, Host-Pathogen Interactions, Staphylococcus epidermidis |
Abstract | CRISPR loci are a cluster of repeats separated by short "spacer" sequences derived from prokaryotic viruses and plasmids that determine the targets of the host's CRISPR-Cas immune response against its invaders. For type I and II CRISPR-Cas systems, single-nucleotide mutations in the seed or protospacer adjacent motif (PAM) of the target sequence cause immune failure and allow viral escape. This is overcome by the acquisition of multiple spacers that target the same invader. Here we show that targeting by the Staphylococcus epidermidis type III-A CRISPR-Cas system does not require PAM or seed sequences, and thus prevents viral escape via single-nucleotide substitutions. Instead, viral escapers can only arise through complete target deletion. Our work shows that, as opposed to type I and II systems, the relaxed specificity of type III CRISPR-Cas targeting provides robust immune responses that can lead to viral extinction with a single spacer targeting an essential phage sequence. |
DOI | 10.1016/j.chom.2017.07.016 |
Alternate Journal | Cell Host Microbe |
PubMed ID | 28826839 |
PubMed Central ID | PMC5599366 |
Grant List | DP2 AI104556 / AI / NIAID NIH HHS / United States R01 CA194547 / CA / NCI NIH HHS / United States T32 GM083937 / GM / NIGMS NIH HHS / United States U24 CA210989 / CA / NCI NIH HHS / United States |