Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

ABSTRACT 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 pn...

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Autores principales:	Jinghui Zhang, Weijie Ye, Kaifeng Wu, Shengnan Xiao, Yuqiang Zheng, Zhaoche Shu, Yibing Yin, Xuemei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Streptococcus pneumoniae capsular polysaccharide phase variation FabT SpnD39III Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/85760a048b7b4be4b97704d086e0c184
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spelling	oai:doaj.org-article:85760a048b7b4be4b97704d086e0c1842021-11-10T18:37:51ZInactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>10.1128/mBio.01304-212150-7511https://doaj.org/article/85760a048b7b4be4b97704d086e0c1842021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01304-21https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Streptococcus pneumoniae is a major human pathogen, and its virulence factors and especially the capsular polysaccharide have been extensively studied. In addition to virulence components that are present on its cell surface that directly interact with the host, S. pneumoniae undergoes a spontaneous and reversible phase variation that allows survival in different host environments. This phase variation is manipulated by the recombination of allelic hsdS genes that encode the sequence recognition proteins of the type I RM system SpnD39III locus. The recombination of hsdS alleles is catalyzed by the DNA invertase PsrA. Interestingly, we found the opaque colony morphology can be reversed by inactivation of the transcriptional regulator FabT, which regulates fatty acid biosynthesis. Inactivation of FabT leads to a significant decrease in capsule production and systematic virulence, but these phase variations do not correlate with the capsule production. This phase variation is mediated via the upregulated invertase PsrA in the ΔfabT mutant. These results identify an unexpected link between the specific phase variations and FabT that strongly suggests an underlying mechanism regulating the DNA invertase PsrA.Jinghui ZhangWeijie YeKaifeng WuShengnan XiaoYuqiang ZhengZhaoche ShuYibing YinXuemei ZhangAmerican Society for MicrobiologyarticleStreptococcus pneumoniaecapsular polysaccharidephase variationFabTSpnD39IIIMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae capsular polysaccharide phase variation FabT SpnD39III Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae capsular polysaccharide phase variation FabT SpnD39III Microbiology QR1-502 Jinghui Zhang Weijie Ye Kaifeng Wu Shengnan Xiao Yuqiang Zheng Zhaoche Shu Yibing Yin Xuemei Zhang Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
description	ABSTRACT 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. IMPORTANCE Streptococcus pneumoniae is a major human pathogen, and its virulence factors and especially the capsular polysaccharide have been extensively studied. In addition to virulence components that are present on its cell surface that directly interact with the host, S. pneumoniae undergoes a spontaneous and reversible phase variation that allows survival in different host environments. This phase variation is manipulated by the recombination of allelic hsdS genes that encode the sequence recognition proteins of the type I RM system SpnD39III locus. The recombination of hsdS alleles is catalyzed by the DNA invertase PsrA. Interestingly, we found the opaque colony morphology can be reversed by inactivation of the transcriptional regulator FabT, which regulates fatty acid biosynthesis. Inactivation of FabT leads to a significant decrease in capsule production and systematic virulence, but these phase variations do not correlate with the capsule production. This phase variation is mediated via the upregulated invertase PsrA in the ΔfabT mutant. These results identify an unexpected link between the specific phase variations and FabT that strongly suggests an underlying mechanism regulating the DNA invertase PsrA.
format	article
author	Jinghui Zhang Weijie Ye Kaifeng Wu Shengnan Xiao Yuqiang Zheng Zhaoche Shu Yibing Yin Xuemei Zhang
author_facet	Jinghui Zhang Weijie Ye Kaifeng Wu Shengnan Xiao Yuqiang Zheng Zhaoche Shu Yibing Yin Xuemei Zhang
author_sort	Jinghui Zhang
title	Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_short	Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full	Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_fullStr	Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_full_unstemmed	Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>
title_sort	inactivation of transcriptional regulator fabt influences colony phase variation of <named-content content-type="genus-species">streptococcus pneumoniae</named-content>
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/85760a048b7b4be4b97704d086e0c184
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Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of <named-content content-type="genus-species">Streptococcus pneumoniae</named-content>

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