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Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity
Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714391/ https://www.ncbi.nlm.nih.gov/pubmed/29155899 http://dx.doi.org/10.1371/journal.ppat.1006729 |
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author | Alteri, Christopher J. Himpsl, Stephanie D. Zhu, Kevin Hershey, Haley L. Musili, Ninette Miller, Jessa E. Mobley, Harry L. T. |
author_facet | Alteri, Christopher J. Himpsl, Stephanie D. Zhu, Kevin Hershey, Haley L. Musili, Ninette Miller, Jessa E. Mobley, Harry L. T. |
author_sort | Alteri, Christopher J. |
collection | PubMed |
description | Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector. |
format | Online Article Text |
id | pubmed-5714391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57143912017-12-15 Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity Alteri, Christopher J. Himpsl, Stephanie D. Zhu, Kevin Hershey, Haley L. Musili, Ninette Miller, Jessa E. Mobley, Harry L. T. PLoS Pathog Research Article Type VI secretion systems (T6SS) function to deliver lethal payloads into target cells. Many studies have shown that protection against a single, lethal T6SS effector protein requires a cognate antidote immunity protein, both of which are often encoded together in a two-gene operon. The T6SS and an effector-immunity pair is sufficient for both killing and immunity. HereIn this paper we describe a T6SS effector operon that differs from conventional effector-immunity pairs in that eight genes are necessary for lethal effector function, yet can be countered by a single immunity protein. In this study, we investigated the role that the PefE T6SS immunity protein plays in recognition between two strains harboring nearly identical effector operons. Interestingly, despite containing seven of eight identical effector proteins, the less conserved immunity proteins only provided protection against their native effectors, suggesting that specificity and recognition could be dependent on variation within an immunity protein and one effector gene product. The variable effector gene product, PefD, is encoded upstream from pefE, and displays toxic activity that can be countered by PefE independent of T6SS-activity. Interestingly, while the entire pef operon was necessary to exert toxic activity via the T6SS in P. mirabilis, production of PefD and PefE alone was unable to exert this effector activity. Chimeric PefE proteins constructed from two P. mirabilis strains were used to localize immunity function to three amino acids. A promiscuous immunity protein was created using site-directed mutagenesis to change these residues from one variant to another. These findings support the notion that subtle differences between conserved effectors are sufficient for T6SS-mediated kin discrimination and that PefD requires additional factors to function as a T6SS-dependent effector. Public Library of Science 2017-11-20 /pmc/articles/PMC5714391/ /pubmed/29155899 http://dx.doi.org/10.1371/journal.ppat.1006729 Text en © 2017 Alteri et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Alteri, Christopher J. Himpsl, Stephanie D. Zhu, Kevin Hershey, Haley L. Musili, Ninette Miller, Jessa E. Mobley, Harry L. T. Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title | Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title_full | Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title_fullStr | Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title_full_unstemmed | Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title_short | Subtle variation within conserved effector operon gene products contributes to T6SS-mediated killing and immunity |
title_sort | subtle variation within conserved effector operon gene products contributes to t6ss-mediated killing and immunity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714391/ https://www.ncbi.nlm.nih.gov/pubmed/29155899 http://dx.doi.org/10.1371/journal.ppat.1006729 |
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