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A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism
Bacterial abortive infection (Abi) systems are ‘altruistic’ cell death systems that are activated by phage infection and limit viral replication, thereby providing protection to the bacterial population. Here, we have used a novel approach of screening Abi systems as a tool to identify and character...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985639/ https://www.ncbi.nlm.nih.gov/pubmed/24465005 http://dx.doi.org/10.1093/nar/gkt1419 |
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author | Dy, Ron L. Przybilski, Rita Semeijn, Koen Salmond, George P.C. Fineran, Peter C. |
author_facet | Dy, Ron L. Przybilski, Rita Semeijn, Koen Salmond, George P.C. Fineran, Peter C. |
author_sort | Dy, Ron L. |
collection | PubMed |
description | Bacterial abortive infection (Abi) systems are ‘altruistic’ cell death systems that are activated by phage infection and limit viral replication, thereby providing protection to the bacterial population. Here, we have used a novel approach of screening Abi systems as a tool to identify and characterize toxin–antitoxin (TA)-acting Abi systems. We show that AbiE systems are encoded by bicistronic operons and function via a non-interacting (Type IV) bacteriostatic TA mechanism. The abiE operon was negatively autoregulated by the antitoxin, AbiEi, a member of a widespread family of putative transcriptional regulators. AbiEi has an N-terminal winged-helix-turn-helix domain that is required for repression of abiE transcription, and an uncharacterized bi-functional C-terminal domain, which is necessary for transcriptional repression and sufficient for toxin neutralization. The cognate toxin, AbiEii, is a predicted nucleotidyltransferase (NTase) and member of the DNA polymerase β family. AbiEii specifically bound GTP, and mutations in conserved NTase motifs (I-III) and a newly identified motif (IV), abolished GTP binding and subsequent toxicity. The AbiE systems can provide phage resistance and enable stabilization of mobile genetic elements, such as plasmids. Our study reveals molecular insights into the regulation and function of the widespread bi-functional AbiE Abi-TA systems and the biochemical properties of both toxin and antitoxin proteins. |
format | Online Article Text |
id | pubmed-3985639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39856392014-04-18 A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism Dy, Ron L. Przybilski, Rita Semeijn, Koen Salmond, George P.C. Fineran, Peter C. Nucleic Acids Res Nucleic Acid Enzymes Bacterial abortive infection (Abi) systems are ‘altruistic’ cell death systems that are activated by phage infection and limit viral replication, thereby providing protection to the bacterial population. Here, we have used a novel approach of screening Abi systems as a tool to identify and characterize toxin–antitoxin (TA)-acting Abi systems. We show that AbiE systems are encoded by bicistronic operons and function via a non-interacting (Type IV) bacteriostatic TA mechanism. The abiE operon was negatively autoregulated by the antitoxin, AbiEi, a member of a widespread family of putative transcriptional regulators. AbiEi has an N-terminal winged-helix-turn-helix domain that is required for repression of abiE transcription, and an uncharacterized bi-functional C-terminal domain, which is necessary for transcriptional repression and sufficient for toxin neutralization. The cognate toxin, AbiEii, is a predicted nucleotidyltransferase (NTase) and member of the DNA polymerase β family. AbiEii specifically bound GTP, and mutations in conserved NTase motifs (I-III) and a newly identified motif (IV), abolished GTP binding and subsequent toxicity. The AbiE systems can provide phage resistance and enable stabilization of mobile genetic elements, such as plasmids. Our study reveals molecular insights into the regulation and function of the widespread bi-functional AbiE Abi-TA systems and the biochemical properties of both toxin and antitoxin proteins. Oxford University Press 2014-04 2014-01-24 /pmc/articles/PMC3985639/ /pubmed/24465005 http://dx.doi.org/10.1093/nar/gkt1419 Text en © The Author(s) 2014. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Nucleic Acid Enzymes Dy, Ron L. Przybilski, Rita Semeijn, Koen Salmond, George P.C. Fineran, Peter C. A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title | A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title_full | A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title_fullStr | A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title_full_unstemmed | A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title_short | A widespread bacteriophage abortive infection system functions through a Type IV toxin–antitoxin mechanism |
title_sort | widespread bacteriophage abortive infection system functions through a type iv toxin–antitoxin mechanism |
topic | Nucleic Acid Enzymes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985639/ https://www.ncbi.nlm.nih.gov/pubmed/24465005 http://dx.doi.org/10.1093/nar/gkt1419 |
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