Evidence map›Paper›PMID 32325050›Full record

ArticleCell host & microbe2020

Listeria Phages Induce Cas9 Degradation to Protect Lysogenic Genomes.

Beatriz A Osuna, Shweta Karambelkar, Caroline Mahendra, Kathleen A Christie, Bianca Garcia, Alan R Davidson, Benjamin P Kleinstiver, Samuel Kilcher, Joseph Bondy-Denomy

Open access · bronzeAbstract readComment
In one paragraph

Article in Cell host & microbe, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 92 citations in OpenAlex.

  1. Revisiting the life cycle of temperate phages.Nature reviews. Microbiology · 2026
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  10. In silico evolution of globular protein folds from random sequences.Proceedings of the National Academy of Sciences of the United States of America · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 3 countries.

Beatriz A OsunaDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Shweta KarambelkarDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Caroline MahendraDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Kathleen A ChristieCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Bianca GarciaDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada.
Alan R DavidsonDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, Canada.
Benjamin P KleinstiverCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Samuel KilcherInstitute of Food, Nutrition, and Health, ETH Zurich, Zurich CH 8092, Switzerland.
Joseph Bondy-DenomyDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Innovative Genomics Institute, Berkeley, CA 94720, USA. Electronic address: joseph.bondy-denomy@ucsf.edu.
University of California, San Francisco · USHarvard University · USUniversity of Toronto · CAETH Zurich · CHQB3 · US

Funding

PROJECT 4: Somatic evolution of the hematopoietic system in cardiovascular diseaseP01HL142494 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Charles P. Lin · 2019 to 2026
$19.5M
Discovering New Roles for CRISPR-Cas in Bacterial PathogenesisDP5OD021344 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BONDY-DENOMY, JOSEPH · 2015 to 2019
$2.1M
Uncovering the mechanism and role of a widespread anti-CRISPR-Cas9 proteinR01GM127489 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BONDY-DENOMY, JOSEPH · 2018 to 2022
$1.7M
Optimizing Cancer Immunotherapy Safety and Efficacy using Genome EditingR00CA218870 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI KLEINSTIVER, BENJAMIN PETER · 2018 to 2020
$730k
NCI NIH HHS R00 CA218870NHLBI NIH HHS P01 HL142494NIGMS NIH HHS R01 GM127489NIH HHS DP5 OD021344
6 · The paper itself

Abstract

Bacterial CRISPR-Cas systems employ RNA-guided nucleases to destroy phage (viral) DNA. Phages, in turn, have evolved diverse "anti-CRISPR" proteins (Acrs) to counteract acquired immunity. In Listeria monocytogenes, prophages encode two to three distinct anti-Cas9 proteins, with acrIIA1 always present. However, the significance of AcrIIA1's pervasiveness and its mechanism are unknown. Here, we report that AcrIIA1 binds with high affinity to Cas9 via the catalytic HNH domain. During lysogeny in Listeria, AcrIIA1 triggers Cas9 degradation. During lytic infection, however, AcrIIA1 fails to block Cas9 due to its multi-step inactivation mechanism. Thus, phages encode an additional Acr that rapidly binds and inactivates Cas9. AcrIIA1 also uniquely inhibits a highly diverged Cas9 found in Listeria (similar to SauCas9) and Type II-C Cas9s, likely due to Cas9 HNH domain conservation. In summary, Listeria phages inactivate Cas9 in lytic growth using variable, narrow-spectrum inhibitors, while the broad-spectrum AcrIIA1 stimulates Cas9 degradation for protection of the lysogenic genome.

Indexed as

ListeriaBacteriophagesClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsLysogenyanti-CRISPRbacteriophageCas9CRISPR-CasListerialysogenprophage

Identifiers

PMID32325050
PMCPMC7351598
OpenAlexW3020430037

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.