Identification of Tse8 as a Type VI secretion system toxin from Pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells.
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Authors
Nolan, Laura M
Clamens, Thomas
Manoli, Eleni
Sainz-Polo, Maria A
Dougan, Gordon
Publication Date
2021-09Journal Title
Nat Microbiol
ISSN
2058-5276
Publisher
Springer Science and Business Media LLC
Volume
6
Issue
9
Pages
1199-1210
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Nolan, L. M., Cain, A. K., Clamens, T., Furniss, R. C. D., Manoli, E., Sainz-Polo, M. A., Dougan, G., et al. (2021). Identification of Tse8 as a Type VI secretion system toxin from Pseudomonas aeruginosa that targets the bacterial transamidosome to inhibit protein synthesis in prey cells.. Nat Microbiol, 6 (9), 1199-1210. https://doi.org/10.1038/s41564-021-00950-8
Abstract
The Type VI secretion system (T6SS) is a bacterial nanomachine that delivers toxic effectors to kill competitors or subvert some of their key functions. Here, we use transposon directed insertion-site sequencing to identify T6SS toxins associated with the H1-T6SS, one of the three T6SS machines found in Pseudomonas aeruginosa. This approach identified several putative toxin-immunity pairs, including Tse8-Tsi8. Full characterization of this protein pair demonstrated that Tse8 is delivered by the VgrG1a spike complex into prey cells where it targets the transamidosome, a multiprotein complex involved in protein synthesis in bacteria that lack either one, or both, of the asparagine and glutamine transfer RNA synthases. Biochemical characterization of the interactions between Tse8 and the transamidosome components GatA, GatB and GatC suggests that the presence of Tse8 alters the fine-tuned stoichiometry of the transamidosome complex, and in vivo assays demonstrate that Tse8 limits the ability of prey cells to synthesize proteins. These data expand the range of cellular components targeted by the T6SS by identifying a T6SS toxin affecting protein synthesis and validate the use of a transposon directed insertion site sequencing-based global genomics approach to expand the repertoire of T6SS toxins in T6SS-encoding bacteria.
Keywords
Bacterial Proteins, Bacterial Toxins, Multiprotein Complexes, Protein Binding, Protein Biosynthesis, Pseudomonas aeruginosa, Type VI Secretion Systems
Identifiers
External DOI: https://doi.org/10.1038/s41564-021-00950-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329580
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