DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25

Aaron Whiteley — Fri, 30 May 2025 15:00:00 +0000

DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25 Aaron Whiteley Fri, 05/30/2025 - 09:00

Amy Conte , Madison Ruchel , Samantha Ridgeway , Emily Kibby , Toni Nagy , Aaron Whiteley

PLoS Biology (2025). PubMed PMID: 40446071; PubMed Central PMCID:

Abstract

Bacteria encode a wide range of antiphage systems and a subset of these proteins are homologous to components of the human innate immune system. Mammalian nucleotide-binding and leucine-rich repeat containing proteins (NLRs) and bacterial NLR-related proteins use a central NACHT domain to link detection of infection with initiation of an antimicrobial response. Bacterial NACHT proteins provide defense against both DNA and RNA phages. Here we investigate the mechanism of phage detection by the bacterial NLR-related protein bNACHT25 in E. coli. bNACHT25 was specifically activated by Emesvirus ssRNA phages and analysis of MS2 phage escaper mutants that evaded detection revealed a critical role for Coat Protein (CP). A genetic assay showed CP was sufficient to activate bNACHT25 but the two proteins did not directly interact. Instead, we found bNACHT25 requires the host chaperone DnaJ to detect CP and protect against phage. Our data support a model in which bNACHT25 detects a wide range of phages using an indirect mechanism that may involve guarding a host cell process rather than binding a specific phage-derived molecule.

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Citation

Conte AN, Ruchel ME, Ridgeway SM, Kibby EM, Nagy TA, Whiteley AT. DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25. PLoS Biol. 2025 May 30;23(5):e3003203. doi: 10.1371/journal.pbio.3003203. [Epub ahead of print] PubMed PMID: 40446071.

Conte AN, Ruchel ME, Ridgeway SM, Kibby EM, Nagy TA, ➤Whiteley, AT | PLoS Biology 2025

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Bacterial NLR-related proteins protect against phage

Anonymous — Mon, 08 May 2023 15:17:54 +0000

Bacterial NLR-related proteins protect against phage Anonymous (not verified) Mon, 05/08/2023 - 09:17

Emily Kibby , Amy Conte , Burroughs AM , Toni Nagy , Alfredo Vargas , Lindsay Whalen , Aravind L , Aaron Whiteley

Cell (2023). PubMed PMID: 37160116; PubMed Central PMCID: PMC10294775.

Abstract

Bacteria use a wide range of immune pathways to counter phage infection. A subset of these genes shares homology with components of eukaryotic immune systems, suggesting that eukaryotes horizontally acquired certain innate immune genes from bacteria. Here, we show that proteins containing a NACHT module, the central feature of the animal nucleotide-binding domain and leucine-rich repeat containing gene family (NLRs), are found in bacteria and defend against phages. NACHT proteins are widespread in bacteria, provide immunity against both DNA and RNA phages, and display the characteristic C-terminal sensor, central NACHT, and N-terminal effector modules. Some bacterial NACHT proteins have domain architectures similar to the human NLRs that are critical components of inflammasomes. Human disease-associated NLR mutations that cause stimulus-independent activation of the inflammasome also activate bacterial NACHT proteins, supporting a shared signaling mechanism. This work establishes that NACHT module-containing proteins are ancient mediators of innate immunity across the tree of life.

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Ancient mediators of innate immunity [SBGrid]
Cross-kingdom defence proteins [Nature Reviews Microbiology]
Read Emily's Tweetorial [Twitter]

Citation

Kibby EM, Conte AN, Burroughs AM, Nagy TA, Vargas JA, Whalen LA, Aravind L, Whiteley AT. Bacterial NLR-related proteins protect against phage. Cell. 2023 May 25;186(11):2410-2424.e18. doi: 10.1016/j.cell.2023.04.015. Epub 2023 May 8. PubMed PMID: 37160116; PubMed Central PMCID: PMC10294775.

Kibby EM, Conte AN, Burroughs AN, Nagy TA, Vargas JA, Whalen LA, Aravind L, ➤Whiteley AT | Cell 2023

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DnaJ mediates phage sensing by the bacterial NLR-related protein bNACHT25

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Bacterial NLR-related proteins protect against phage

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