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

Autor: Stoltzfus MJ; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Workman RE; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Keith NC; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Modell JW; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jmodell1@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Sep; Vol. 9 (9), pp. 2410-2421. Date of Electronic Publication: 2024 Jul 12.
DOI: 10.1038/s41564-024-01748-0
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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