puc-header

CRISPR-Cas Immune System of a Prevalent Human Gut Bacterium Reveals Hypertargeting Against Gut Virome Phages

47 Pages Posted: 2 Apr 2019 Sneak Peek Status: Published

See all articles by Paola Soto-Perez

Paola Soto-Perez

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Jordan E. Bisanz

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Joel D. Berry

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Kathy N. Lam

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Joseph Bondy-Denomy

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology; University of California, San Francisco (UCSF) - Quantitative Biosciences Institute

Peter Turnbaugh

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology; Chan Zuckerberg Biohub

More...

Abstract

Bacteriophages are the most abundant entities found within the human gastrointestinal tract, yettheir interaction with bacterial hosts remain poorly understood, particularly with respect to CRISPRCas immunity. Here, we show that the Type IC CRISPRCas system in the prevalent gut Actinobacterium Eggerthella lenta i s active both transcriptionally and catalytically, cleaving foreign and self DNA. Comparative analyses of E. lenta CRISPRCas systems across genomes and metagenomes revealed two distinct clades according to their shared cas gene sequence similarity and spacer content. To identify putative CRISPR targets, we assembled a human virome database (HuVirDB) encompassing 1,831 samples, revealing matches for the majority of the identified spacers, including “hypertargeted” phage with as many as 96 protospacers. Modeling observed spacer/protospacer pairs, we mapped positional mismatch tolerance in crRNAs. This work emphasizes the utility of merging computational and experimental approaches for determining the function and targets of human gut bacterial CRISPRCas systems.

Keywords: human microbiome, CRISPR-Cas systems, bacteriophage, virome, heterologous expression, hyper-targeting

Suggested Citation

Soto-Perez, Paola and Bisanz, Jordan E. and Berry, Joel D. and Lam, Kathy N. and Bondy-Denomy, Joseph and Turnbaugh, Peter, CRISPR-Cas Immune System of a Prevalent Human Gut Bacterium Reveals Hypertargeting Against Gut Virome Phages (April 1, 2019). Available at SSRN: https://ssrn.com/abstract=3363840 or http://dx.doi.org/10.2139/ssrn.3363840
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Paola Soto-Perez

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Jordan E. Bisanz

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

San Francisco, CA 94143
United States

Joel D. Berry

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Kathy N. Lam

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Joseph Bondy-Denomy

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Quantitative Biosciences Institute

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Peter Turnbaugh (Contact Author)

University of California, San Francisco (UCSF) - Department of Microbiology and Immunology ( email )

San Francisco, CA 94143
United States

Chan Zuckerberg Biohub ( email )

499 Illinois Street
San Francisco, CA 94158
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
438
Downloads
22