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Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins

Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is transl...

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Autores principales: Song, Nan, Chen, Lihong, Zhou, Zhemin, Ren, Xingmei, Liu, Bo, Zhou, Siyu, Wang, Caihong, Wu, Yun, Waterfield, Nicholas R., Yang, Jian, Yang, Guowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861908/
https://www.ncbi.nlm.nih.gov/pubmed/33540421
http://dx.doi.org/10.1371/journal.ppat.1009102
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author Song, Nan
Chen, Lihong
Zhou, Zhemin
Ren, Xingmei
Liu, Bo
Zhou, Siyu
Wang, Caihong
Wu, Yun
Waterfield, Nicholas R.
Yang, Jian
Yang, Guowei
author_facet Song, Nan
Chen, Lihong
Zhou, Zhemin
Ren, Xingmei
Liu, Bo
Zhou, Siyu
Wang, Caihong
Wu, Yun
Waterfield, Nicholas R.
Yang, Jian
Yang, Guowei
author_sort Song, Nan
collection PubMed
description Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits. Currently the pathogenic roles and distribution of Tc toxins among different bacterial genera remain unclear. Here we have performed a comprehensive genome-wide analysis, and established a database that includes 1,608 identified Tc loci containing 2,528 TcC proteins in 1,421 Gram-negative and positive bacterial genomes. Our findings indicate that TcCs conform to the architecture of typical polymorphic toxins, with C-terminal hypervariable regions (HVR) encoding more than 100 different classes of putative toxic domains, most of which have not been previously recognized. Based on further analysis of Tc loci in the genomes of all Salmonella and Yersinia strains in EnteroBase, a “two-level” evolutionary dynamics scenario is proposed for TcC homologues. This scenario implies that the conserved TcC RHS core domain plays a critical role in the taxonomical specific distribution of TcC HVRs. This study provides an extensive resource for the future development of Tc toxins as valuable agrochemical tools. It furthermore implies that Tc proteins, which are encoded by a wide range of pathogens, represent an important versatile toxin superfamily with diverse pathogenic mechanisms.
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spelling pubmed-78619082021-02-12 Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins Song, Nan Chen, Lihong Zhou, Zhemin Ren, Xingmei Liu, Bo Zhou, Siyu Wang, Caihong Wu, Yun Waterfield, Nicholas R. Yang, Jian Yang, Guowei PLoS Pathog Research Article Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits. Currently the pathogenic roles and distribution of Tc toxins among different bacterial genera remain unclear. Here we have performed a comprehensive genome-wide analysis, and established a database that includes 1,608 identified Tc loci containing 2,528 TcC proteins in 1,421 Gram-negative and positive bacterial genomes. Our findings indicate that TcCs conform to the architecture of typical polymorphic toxins, with C-terminal hypervariable regions (HVR) encoding more than 100 different classes of putative toxic domains, most of which have not been previously recognized. Based on further analysis of Tc loci in the genomes of all Salmonella and Yersinia strains in EnteroBase, a “two-level” evolutionary dynamics scenario is proposed for TcC homologues. This scenario implies that the conserved TcC RHS core domain plays a critical role in the taxonomical specific distribution of TcC HVRs. This study provides an extensive resource for the future development of Tc toxins as valuable agrochemical tools. It furthermore implies that Tc proteins, which are encoded by a wide range of pathogens, represent an important versatile toxin superfamily with diverse pathogenic mechanisms. Public Library of Science 2021-02-04 /pmc/articles/PMC7861908/ /pubmed/33540421 http://dx.doi.org/10.1371/journal.ppat.1009102 Text en © 2021 Song 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
Song, Nan
Chen, Lihong
Zhou, Zhemin
Ren, Xingmei
Liu, Bo
Zhou, Siyu
Wang, Caihong
Wu, Yun
Waterfield, Nicholas R.
Yang, Jian
Yang, Guowei
Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title_full Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title_fullStr Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title_full_unstemmed Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title_short Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins
title_sort genome-wide dissection reveals diverse pathogenic roles of bacterial tc toxins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861908/
https://www.ncbi.nlm.nih.gov/pubmed/33540421
http://dx.doi.org/10.1371/journal.ppat.1009102
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