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VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system

The type VI secretion system (T6SS) is a spear-like nanomachine found in gram-negative pathogens for delivery of toxic effectors to neighboring bacterial and host cells. Its assembly requires a tip spike complex consisting of a VgrG-trimer, a PAAR protein, and the interacting effectors. However, how...

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Autores principales: Liang, Xiaoye, Pei, Tong-Tong, Li, Hao, Zheng, Hao-Yu, Luo, Han, Cui, Yang, Tang, Ming-Xuan, Zhao, Ya-Jie, Xu, Ping, Dong, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668125/
https://www.ncbi.nlm.nih.gov/pubmed/34852023
http://dx.doi.org/10.1371/journal.ppat.1010116
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author Liang, Xiaoye
Pei, Tong-Tong
Li, Hao
Zheng, Hao-Yu
Luo, Han
Cui, Yang
Tang, Ming-Xuan
Zhao, Ya-Jie
Xu, Ping
Dong, Tao
author_facet Liang, Xiaoye
Pei, Tong-Tong
Li, Hao
Zheng, Hao-Yu
Luo, Han
Cui, Yang
Tang, Ming-Xuan
Zhao, Ya-Jie
Xu, Ping
Dong, Tao
author_sort Liang, Xiaoye
collection PubMed
description The type VI secretion system (T6SS) is a spear-like nanomachine found in gram-negative pathogens for delivery of toxic effectors to neighboring bacterial and host cells. Its assembly requires a tip spike complex consisting of a VgrG-trimer, a PAAR protein, and the interacting effectors. However, how the spike controls T6SS assembly remains elusive. Here we investigated the role of three VgrG-effector pairs in Aeromonas dhakensis strain SSU, a clinical isolate with a constitutively active T6SS. By swapping VgrG tail sequences, we demonstrate that the C-terminal ~30 amino-acid tail dictates effector specificity. Double deletion of vgrG1&2 genes (VgrG3(+)) abolished T6SS secretion, which can be rescued by ectopically expressing chimeric VgrG3 with a VgrG1/2-tail but not the wild type VgrG3. In addition, deletion of effector-specific chaperones also severely impaired T6SS secretion, despite the presence of intact VgrG and effector proteins, in both SSU and Vibrio cholerae V52. We further show that SSU could deliver a V. cholerae effector VasX when expressing a plasmid-borne chimeric VgrG with VasX-specific VgrG tail and chaperone sequences. Pull-down analyses show that two SSU effectors, TseP and TseC, could interact with their cognate VgrGs, the baseplate protein TssK, and the key assembly chaperone TssA. Effectors TseL and VasX could interact with TssF, TssK and TssA in V. cholerae. Collectively, we demonstrate that chimeric VgrG-effector pairs could bypass the requirement of heterologous VgrG complex and propose that effector-stuffing inside the baseplate complex, facilitated by chaperones and the interaction with structural proteins, serves as a crucial structural determinant for T6SS assembly.
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spelling pubmed-86681252021-12-14 VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system Liang, Xiaoye Pei, Tong-Tong Li, Hao Zheng, Hao-Yu Luo, Han Cui, Yang Tang, Ming-Xuan Zhao, Ya-Jie Xu, Ping Dong, Tao PLoS Pathog Research Article The type VI secretion system (T6SS) is a spear-like nanomachine found in gram-negative pathogens for delivery of toxic effectors to neighboring bacterial and host cells. Its assembly requires a tip spike complex consisting of a VgrG-trimer, a PAAR protein, and the interacting effectors. However, how the spike controls T6SS assembly remains elusive. Here we investigated the role of three VgrG-effector pairs in Aeromonas dhakensis strain SSU, a clinical isolate with a constitutively active T6SS. By swapping VgrG tail sequences, we demonstrate that the C-terminal ~30 amino-acid tail dictates effector specificity. Double deletion of vgrG1&2 genes (VgrG3(+)) abolished T6SS secretion, which can be rescued by ectopically expressing chimeric VgrG3 with a VgrG1/2-tail but not the wild type VgrG3. In addition, deletion of effector-specific chaperones also severely impaired T6SS secretion, despite the presence of intact VgrG and effector proteins, in both SSU and Vibrio cholerae V52. We further show that SSU could deliver a V. cholerae effector VasX when expressing a plasmid-borne chimeric VgrG with VasX-specific VgrG tail and chaperone sequences. Pull-down analyses show that two SSU effectors, TseP and TseC, could interact with their cognate VgrGs, the baseplate protein TssK, and the key assembly chaperone TssA. Effectors TseL and VasX could interact with TssF, TssK and TssA in V. cholerae. Collectively, we demonstrate that chimeric VgrG-effector pairs could bypass the requirement of heterologous VgrG complex and propose that effector-stuffing inside the baseplate complex, facilitated by chaperones and the interaction with structural proteins, serves as a crucial structural determinant for T6SS assembly. Public Library of Science 2021-12-01 /pmc/articles/PMC8668125/ /pubmed/34852023 http://dx.doi.org/10.1371/journal.ppat.1010116 Text en © 2021 Liang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Liang, Xiaoye
Pei, Tong-Tong
Li, Hao
Zheng, Hao-Yu
Luo, Han
Cui, Yang
Tang, Ming-Xuan
Zhao, Ya-Jie
Xu, Ping
Dong, Tao
VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title_full VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title_fullStr VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title_full_unstemmed VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title_short VgrG-dependent effectors and chaperones modulate the assembly of the type VI secretion system
title_sort vgrg-dependent effectors and chaperones modulate the assembly of the type vi secretion system
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668125/
https://www.ncbi.nlm.nih.gov/pubmed/34852023
http://dx.doi.org/10.1371/journal.ppat.1010116
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