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Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae
Streptococcus pneumoniae is an opportunistic pathogen that can alter its cell surface phenotype in response to the host environment. We demonstrated that the transcriptional regulator FabT is an indirect regulator of capsular polysaccharide, an important virulence factor of Streptococcus pneumoniae....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406281/ https://www.ncbi.nlm.nih.gov/pubmed/34399624 http://dx.doi.org/10.1128/mBio.01304-21 |
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author | Zhang, Jinghui Ye, Weijie Wu, Kaifeng Xiao, Shengnan Zheng, Yuqiang Shu, Zhaoche Yin, Yibing Zhang, Xuemei |
author_facet | Zhang, Jinghui Ye, Weijie Wu, Kaifeng Xiao, Shengnan Zheng, Yuqiang Shu, Zhaoche Yin, Yibing Zhang, Xuemei |
author_sort | Zhang, Jinghui |
collection | PubMed |
description | Streptococcus pneumoniae is an opportunistic pathogen that can alter its cell surface phenotype in response to the host environment. We demonstrated that the transcriptional regulator FabT is an indirect regulator of capsular polysaccharide, an important virulence factor of Streptococcus pneumoniae. Transcriptome analysis between the wild-type D39s and D39ΔfabT mutant strains unexpectedly identified a differentially expressed gene encoding a site-specific recombinase, PsrA. PsrA catalyzes the inversion of 3 homologous hsdS genes in a type I restriction-modification (RM) system SpnD39III locus and is responsible for the reversible switch of phase variation. Our study demonstrated that upregulation of PsrA in a D39ΔfabT mutant correlated with an increased ratio of transparent (T) phase variants. Inactivation of the invertase PsrA led to uniform opaque (O) variants. Direct quantification of allelic variants of hsdS derivatives and inversions of inverted repeats indicated that the recombinase PsrA fully catalyzes the inversion mediated by IR1 and IR3, and FabT mediated the recombination of the hsdS alleles in PsrA-dependent and PsrA-independent manners. In addition, compared to D39s, the ΔfabT mutant exhibited reduced nasopharyngeal colonization and was more resistant to phagocytosis and less adhesive to epithelial cells. These results indicated that phase variation in the ΔfabT mutant also affects other cell surface components involved in host interactions. |
format | Online Article Text |
id | pubmed-8406281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-84062812021-09-09 Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae Zhang, Jinghui Ye, Weijie Wu, Kaifeng Xiao, Shengnan Zheng, Yuqiang Shu, Zhaoche Yin, Yibing Zhang, Xuemei mBio Research Article Streptococcus pneumoniae is an opportunistic pathogen that can alter its cell surface phenotype in response to the host environment. We demonstrated that the transcriptional regulator FabT is an indirect regulator of capsular polysaccharide, an important virulence factor of Streptococcus pneumoniae. Transcriptome analysis between the wild-type D39s and D39ΔfabT mutant strains unexpectedly identified a differentially expressed gene encoding a site-specific recombinase, PsrA. PsrA catalyzes the inversion of 3 homologous hsdS genes in a type I restriction-modification (RM) system SpnD39III locus and is responsible for the reversible switch of phase variation. Our study demonstrated that upregulation of PsrA in a D39ΔfabT mutant correlated with an increased ratio of transparent (T) phase variants. Inactivation of the invertase PsrA led to uniform opaque (O) variants. Direct quantification of allelic variants of hsdS derivatives and inversions of inverted repeats indicated that the recombinase PsrA fully catalyzes the inversion mediated by IR1 and IR3, and FabT mediated the recombination of the hsdS alleles in PsrA-dependent and PsrA-independent manners. In addition, compared to D39s, the ΔfabT mutant exhibited reduced nasopharyngeal colonization and was more resistant to phagocytosis and less adhesive to epithelial cells. These results indicated that phase variation in the ΔfabT mutant also affects other cell surface components involved in host interactions. American Society for Microbiology 2021-08-17 /pmc/articles/PMC8406281/ /pubmed/34399624 http://dx.doi.org/10.1128/mBio.01304-21 Text en Copyright © 2021 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Jinghui Ye, Weijie Wu, Kaifeng Xiao, Shengnan Zheng, Yuqiang Shu, Zhaoche Yin, Yibing Zhang, Xuemei Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title | Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title_full | Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title_fullStr | Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title_full_unstemmed | Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title_short | Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae |
title_sort | inactivation of transcriptional regulator fabt influences colony phase variation of streptococcus pneumoniae |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406281/ https://www.ncbi.nlm.nih.gov/pubmed/34399624 http://dx.doi.org/10.1128/mBio.01304-21 |
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