Nature communicationsAug 31, 2026

Balance between CRISPR immune defense and plasmid resistance controlled by a dual-function protein AcrIE10

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Updated Sep 2, 2026

Abstract

Antimicrobial resistance plasmids are prevalent in clinical isolates of carbapenem-resistant Klebsiella pneumoniae.

CRISPR-Cas systems are targeted by antimicrobial resistance plasmids, posing a significant public health threat.
The co-existence of plasmids and CRISPR-Cas systems is maintained by anti-CRISPR (Acr) proteins.
AcrIE10, an Acr protein, inhibits CRISPR immunity by binding to the Cas7* subunit.
AcrIE10 also functions as an Acr-associated (Aca) protein that represses its own transcription.
Its N-terminal domain recognizes a specific region in its promoter for self-repression.
Dimerization of AcrIE10 is necessary for effective promoter binding and transitioning to a de-repressed state.

Simplified

Despite targeting by CRISPR-Cas system, antimicrobial resistance plasmids are prevalent in clinical isolates of carbapenem-resistant Klebsiella pneumoniae which represent a major public health threat. A stable co-existence of plasmids and CRISPR-Cas systems is mediated by anti-CRISPR (Acr) proteins. Here, we report that previously identified AcrIE10 encoded by a resistance plasmid combines two functions: it inhibits CRISPR immunity by directly binding Cas7 subunit through its Acr domain, and acts as an Acr-associated (Aca) protein that self-represses the transcription of Acr locus. AcrIE10 is an example of an Aca protein that utilizes N-terminal ribbon-helix-helix (RHH) domain to specifically recognize the inverted repeat (IR) region in its own promoter. Crucially, a dimerization of AcrIE10 dimers is required for the effective binding to the IR and self-repression, while stoichiometry-dependent interaction with Cas7 facilitates transition to de-repressed state. These findings elucidate molecular mechanisms by which AcrIE10 operates as a dual functionAcr-Aca protein to achieve a delicate balance between host CRISPR-Cas immunity and plasmid anti-defense.

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Balance between CRISPR immune defense and plasmid resistance controlled by a dual-function protein AcrIE10

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