Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Dy, Ron L., Przybilski, Rita, Semeijn, Koen, Salmond, George P.C., Fineran, Peter C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
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
_version_ 1782311600851517440
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
work_keys_str_mv AT dyronl awidespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT przybilskirita awidespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT semeijnkoen awidespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT salmondgeorgepc awidespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT fineranpeterc awidespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT dyronl widespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT przybilskirita widespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT semeijnkoen widespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT salmondgeorgepc widespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism
AT fineranpeterc widespreadbacteriophageabortiveinfectionsystemfunctionsthroughatypeivtoxinantitoxinmechanism