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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....

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Autores principales: Zhang, Jinghui, Ye, Weijie, Wu, Kaifeng, Xiao, Shengnan, Zheng, Yuqiang, Shu, Zhaoche, Yin, Yibing, Zhang, Xuemei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
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.
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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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