10.6084/M9.FIGSHARE.21154901.V1
Gang Zhao
Gang
Zhao
Doukun Lu
Doukun
Lu
Shujuan Wang
Shujuan
Wang
Hui Zhang
Hui
Zhang
Xifang Zhu
Xifang
Zhu
Zhiyu Hao
Zhiyu
Hao
Ali Dawood
Ali
Dawood
Yingyu Chen
Yingyu
Chen
Elise Schieck
Elise
Schieck
Changmin Hu
Changmin
Hu
Xi Chen
Xi
Chen
Liguo Yang
Liguo
Yang
Aizhen Guo
Aizhen
Guo
Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2
<p>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. <i>Mycoplasma bovis</i> 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 <i>in silico</i> screening, the nuclear localization of the secreted putative lipoprotein MbovP475 of <i>M. bovis</i> was demonstrated in bovine macrophage cell line (BoMac) experimentally infected with <i>M. bovis</i>. 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 <i>CRYAB</i> and <i>MCF2L2</i>. 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 <sup>242</sup>NI<sup>243</sup> 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 <i>M. bovis</i> secretes a conserved TALE-like nucleomodulin that binds the promoters of <i>CRYAB</i> and <i>MCF2L2</i> genes, and subsequently down-regulates their expression and decreases BoMac cell viability. Therefore, this study offers a new understanding of mycoplasma pathogenesis.</p>
Biochemistry
Microbiology
Cell Biology
Genetics
Molecular Biology
Biotechnology
Chemical Sciences not elsewhere classified
Immunology
Biological Sciences not elsewhere classified
Developmental Biology
Cancer
Hematology
Infectious Diseases
Virology
Computational Biology
Taylor & Francis
2022
2022-09-19
2024-03-21
Dataset
20556659 Bytes
10.6084/m9.figshare.21154901
10.1080/21505594.2022.2117762
CC BY 4.0