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CRISPR-Cas system of a prevalent human gut bacterium reveals hyper-targeting against phages in a human virome catalog

Citation

Bisanz, Jordan E. et al. (2021), CRISPR-Cas system of a prevalent human gut bacterium reveals hyper-targeting against phages in a human virome catalog, Dryad, Dataset, https://doi.org/10.7272/Q6FX77PX

Abstract

Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a human virome database (HuVirDB), encompassing 1,831 samples enriched for viral DNA, to identify protospacers. This revealed matches for a majority of spacers, a marked increase over other databases, and uncovered “hyper-targeted” phage sequences containing multiple protospacers targeted by several E. lenta strains. Finally, we determined the positional mismatch tolerance of observed spacer-protospacer pairs. This work emphasizes the utility of merging computational and experimental approaches for determining the function and targets of CRISPR-Cas systems.

Methods

This dataset is a the result of collecting and assembling human metagenomic virome sequencing for the purposes of meta-analysis.

Usage Notes

All scaffolds are identified by their SampleID with metadata available at the associated github repository: https://github.com/jbisanz/HuVirDB.