CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog

Paola Soto-Perez, Jordan E. Bisanz, Joel D. Berry, Kathy N. Lam, Joseph Bondy-Denomy, Peter J. Turnbaugh

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)325-335.e5
JournalCell Host and Microbe
Volume26
Issue number3
DOIs
StatePublished - Sep 11 2019

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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