The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA
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nihms-1813024.pdf
Description
Accepted version
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5.06 MB
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Author(s)
LeRoux, Michele
Srikant, Sriram
Teodoro, Gabriella IC
Zhang, Tong
Littlehale, Megan L
Doron, Shany
Badiee, Mohsen
Leung, Anthony KL
Sorek, Rotem
Laub, Michael T
Date Issued
2022
Journal
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Citation
LeRoux, Michele, Srikant, Sriram, Teodoro, Gabriella IC, Zhang, Tong, Littlehale, Megan L et al. 2022. "The DarTG toxin-antitoxin system provides phage defence by ADP-ribosylating viral DNA." Nature Microbiology, 7 (7).
Version
Author's final manuscript
Abstract
Toxin-antitoxin (TA) systems are broadly distributed, yet poorly conserved, genetic elements whose biological functions are unclear and controversial. Some TA systems may provide bacteria with immunity to infection by their ubiquitous viral predators, bacteriophages. To identify such TA systems, we searched bioinformatically for those frequently encoded near known phage defence genes in bacterial genomes. This search identified homologues of DarTG, a recently discovered family of TA systems whose biological functions and natural activating conditions were unclear. Representatives from two different subfamilies, DarTG1 and DarTG2, strongly protected E. coli MG1655 against different phages. We demonstrate that for each system, infection with either RB69 or T5 phage, respectively, triggers release of the DarT toxin, a DNA ADP-ribosyltransferase, that then modifies viral DNA and prevents replication, thereby blocking the production of mature virions. Further, we isolated phages that have evolved to overcome DarTG defence either through mutations to their DNA polymerase or to an anti-DarT factor, gp61.2, encoded by many T-even phages. Collectively, our results indicate that phage defence may be a common function for TA systems and reveal the mechanism by which DarTG systems inhibit phage infection.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
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DOI of Published Version
https://doi.org/10.1038/S41564-022-01153-5
