Cell host & microbeMar 19, 2026

Human gut viruses produce proteins that help them avoid type II CRISPR immune defense in different ways

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Human gut phages encode a large, diverse set of anti-CRISPR proteins that can block type II CRISPR immunity.

Evidence

This bioinformatics and high-throughput functional screen identified 651 gut phage Acr candidates, verified a subset by plasmid interference, and confirmed CRISPR-Cas inhibitory activity for 36 candidates by plaque assays.

Caveat

Only selected candidates received mechanistic characterization, and biotechnology potential remains inferred from screening and assay data.

Simplified

Phages encode diverse anti-CRISPR (Acr) proteins to counteract bacterial CRISPR-Cas systems. However, gut phage Acrs remain poorly characterized. Using an integrated bioinformatics and high-throughput functional screening approach, we identify 651 phage-encoded positive Acr candidates that target type II CRISPR systems, which predominate in the human gut. Among these, a subset of Acrs is verified through plasmid interference assays, with plaque assays confirming CRISPR-Cas inhibitory activity for 36 Acr candidates. Mechanistic characterization of five Acrs, including the Acr against subtype II-B systems (AcrIIB-1), reveals distinct inhibition strategies. Remarkably, 213 positive Acr candidates, designated here as GutAcr, exhibit structural convergence by adopting similar folds and exhibit dual functionality: transcription regulation to support their production and inhibition of CRISPR-Cas systems. These GutAcrare widely distributed across microbial species (detected in 26% of species). Our work uncovers the extensive diversity of phage-encoded Acrs in the human gut and highlights their potential as biotechnology tools. aca aca