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Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2

Nucleomodulins are secreted bacterial proteins whose molecular targets are located in host cell nuclei. They are gaining attention as critical virulence factors that either modify the epigenetics of host cells or directly regulate host gene expression. Mycoplasma bovis is a major veterinary pathogen...

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Autores principales: Zhao, Gang, Lu, Doukun, Wang, Shujuan, Zhang, Hui, Zhu, Xifang, Hao, Zhiyu, Dawood, Ali, Chen, Yingyu, Schieck, Elise, Hu, Changmin, Chen, Xi, Yang, Liguo, Guo, Aizhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487752/
https://www.ncbi.nlm.nih.gov/pubmed/36121023
http://dx.doi.org/10.1080/21505594.2022.2117762
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author Zhao, Gang
Lu, Doukun
Wang, Shujuan
Zhang, Hui
Zhu, Xifang
Hao, Zhiyu
Dawood, Ali
Chen, Yingyu
Schieck, Elise
Hu, Changmin
Chen, Xi
Yang, Liguo
Guo, Aizhen
author_facet Zhao, Gang
Lu, Doukun
Wang, Shujuan
Zhang, Hui
Zhu, Xifang
Hao, Zhiyu
Dawood, Ali
Chen, Yingyu
Schieck, Elise
Hu, Changmin
Chen, Xi
Yang, Liguo
Guo, Aizhen
author_sort Zhao, Gang
collection PubMed
description Nucleomodulins are secreted bacterial proteins whose molecular targets are located in host cell nuclei. They are gaining attention as critical virulence factors that either modify the epigenetics of host cells or directly regulate host gene expression. Mycoplasma bovis is a major veterinary pathogen that secretes several potential virulence factors. The aim of this study was to determine whether any of their secreted proteins might function as nucleomodulins. After an initial in silico screening, the nuclear localization of the secreted putative lipoprotein MbovP475 of M. bovis was demonstrated in bovine macrophage cell line (BoMac) experimentally infected with M. bovis. Through combined application of ChIP-seq, Electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR) analysis, MbovP475 was determined to bind the promoter regions of the cell cycle central regulatory genes CRYAB and MCF2L2. MbovP475 has similar secondary structures with the transcription activator-like effectors (TALEs). Screening of various mutants affecting the potential DNA binding sites indicated that the residues (242)NI(243) within MbovP475 loop region of the helix-loop-helix domain were essential to its DNA binding activity, thereby contributing to decrease in BoMac cell viability. In conclusion, this is the first report to confirm M. bovis secretes a conserved TALE-like nucleomodulin that binds the promoters of CRYAB and MCF2L2 genes, and subsequently down-regulates their expression and decreases BoMac cell viability. Therefore, this study offers a new understanding of mycoplasma pathogenesis.
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spelling pubmed-94877522022-09-21 Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2 Zhao, Gang Lu, Doukun Wang, Shujuan Zhang, Hui Zhu, Xifang Hao, Zhiyu Dawood, Ali Chen, Yingyu Schieck, Elise Hu, Changmin Chen, Xi Yang, Liguo Guo, Aizhen Virulence Research Paper Nucleomodulins are secreted bacterial proteins whose molecular targets are located in host cell nuclei. They are gaining attention as critical virulence factors that either modify the epigenetics of host cells or directly regulate host gene expression. Mycoplasma bovis is a major veterinary pathogen that secretes several potential virulence factors. The aim of this study was to determine whether any of their secreted proteins might function as nucleomodulins. After an initial in silico screening, the nuclear localization of the secreted putative lipoprotein MbovP475 of M. bovis was demonstrated in bovine macrophage cell line (BoMac) experimentally infected with M. bovis. Through combined application of ChIP-seq, Electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR) analysis, MbovP475 was determined to bind the promoter regions of the cell cycle central regulatory genes CRYAB and MCF2L2. MbovP475 has similar secondary structures with the transcription activator-like effectors (TALEs). Screening of various mutants affecting the potential DNA binding sites indicated that the residues (242)NI(243) within MbovP475 loop region of the helix-loop-helix domain were essential to its DNA binding activity, thereby contributing to decrease in BoMac cell viability. In conclusion, this is the first report to confirm M. bovis secretes a conserved TALE-like nucleomodulin that binds the promoters of CRYAB and MCF2L2 genes, and subsequently down-regulates their expression and decreases BoMac cell viability. Therefore, this study offers a new understanding of mycoplasma pathogenesis. Taylor & Francis 2022-09-19 /pmc/articles/PMC9487752/ /pubmed/36121023 http://dx.doi.org/10.1080/21505594.2022.2117762 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://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/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Zhao, Gang
Lu, Doukun
Wang, Shujuan
Zhang, Hui
Zhu, Xifang
Hao, Zhiyu
Dawood, Ali
Chen, Yingyu
Schieck, Elise
Hu, Changmin
Chen, Xi
Yang, Liguo
Guo, Aizhen
Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title_full Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title_fullStr Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title_full_unstemmed Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title_short Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
title_sort novel mycoplasma nucleomodulin mbovp475 decreased cell viability by regulating expression of cryab and mcf2l2
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487752/
https://www.ncbi.nlm.nih.gov/pubmed/36121023
http://dx.doi.org/10.1080/21505594.2022.2117762
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