Evidence map›Paper›PMID 38997519›Full record

ArticleNature microbiology2024

A dynamic subpopulation of CRISPR-Cas overexpressers allows Streptococcus pyogenes to rapidly respond to phage.

Marie J Stoltzfus, Rachael E Workman, Nicholas C Keith, Joshua W Modell

Abstract read
In one paragraph

Article in Nature microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Marie J StoltzfusDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-5947-3425
Rachael E WorkmanDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nicholas C KeithDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-4050-9261
Joshua W ModellDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jmodell1@jhmi.edu.ORCID http://orcid.org/0000-0001-7733-1252

Funding

Non-canonical functions of Cas9 andthe cell biology of CRISPR-Cas immunityR35GM142731 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Joshua Modell · 2021 to 2026
$2.6M
NIGMS NIH HHS R35 GM142731Rita Allen Foundation (RAF) 90094894U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM142731
6 · The paper itself

Abstract

Many CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein) systems, which provide bacteria with adaptive immunity against phages, are transcriptionally repressed in their native hosts. How CRISPR-Cas expression is induced as needed, for example, during a bacteriophage infection, remains poorly understood. In Streptococcus pyogenes, a non-canonical guide RNA tracr-L directs Cas9 to autorepress its own promoter. Here we describe a dynamic subpopulation of cells harbouring single mutations that disrupt Cas9 binding and cause CRISPR-Cas overexpression. Cas9 actively expands this population by elevating mutation rates at the tracr-L target site. Overexpressers show higher rates of memory formation, stronger potency of old memories and a larger memory storage capacity relative to wild-type cells, which are surprisingly vulnerable to phage infection. However, in the absence of phage, CRISPR-Cas overexpression reduces fitness. We propose that CRISPR-Cas overexpressers are critical players in phage defence, enabling bacterial populations to mount rapid transcriptional responses to phage without requiring transient changes in any one cell.

Indexed as

BacteriophagesCRISPR-Cas SystemsStreptococcus pyogenesClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9Gene Expression Regulation, BacterialMutationPromoter Regions, GeneticRNA, Guide, CRISPR-Cas SystemsStreptococcus PhagesCRISPR-Associated Protein 9RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID38997519
PMCPMC11983678

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Registered trials

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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.