<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes

ABSTRACT Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host env...

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Autores principales:	Melissa B. Oliver, Ankita Basu Roy, Ranjit Kumar, Elliot J. Lefkowitz, W. Edward Swords
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Streptococcus pneumoniae phase variation pneumococcus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d7a553d2d0094ca295946d425fc9e4f5
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spelling	oai:doaj.org-article:d7a553d2d0094ca295946d425fc9e4f52021-11-15T15:21:52Z<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes10.1128/mSphere.00386-172379-5042https://doaj.org/article/d7a553d2d0094ca295946d425fc9e4f52017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00386-17https://doaj.org/toc/2379-5042ABSTRACT Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization, whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression. A panel of isogenic strains were created in the well-studied S. pneumoniae TIGR4 background that are “locked” in the transparent (n = 4) or opaque (n = 2) colony phenotype. The strains had significant differences in colony size which were stable over multiple passages in vitro and in vivo. While there were no significant differences in adherence for the phase-locked mutant strains to immortalized epithelial cells, biofilm formation and viability were reduced for the opaque variants in static assays. Nasopharyngeal colonization was stable for all strains, but the mortality rates differed between them. Transcript profiling by transcriptome sequencing (RNA-seq) analyses revealed that the expression levels of certain virulence factors were increased in a phase-specific manner. As epigenetic regulation of phase variation (often referred to as "phasevarion") is emerging as a common theme for mucosal pathogens, these results serve as a model for future studies of host-pathogen interactions. IMPORTANCE A growing number of bacterial species undergo epigenetic phase variation due to variable expression or specificity of DNA-modifying enzymes. For pneumococci, this phase variation has long been appreciated as being revealed by changes in colony opacity, which are reflected in changes in expression or accessibility of factors on the bacterial surface. Recent work showed that recombination-generated variation in alleles of the HsdS DNA methylase specificity subunit mediated pneumococcal phase variation. We generated phase-locked populations of S. pneumoniae TIGR4 expressing a single nonvariant hsdS allele and observed significant differences in gene expression and virulence. These results highlight the importance of focused pathogenesis studies within specific phase types. Moreover, the generation of single-allele hsdS constructs will greatly facilitate such studies.Melissa B. OliverAnkita Basu RoyRanjit KumarElliot J. LefkowitzW. Edward SwordsAmerican Society for MicrobiologyarticleStreptococcus pneumoniaephase variationpneumococcusMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae phase variation pneumococcus Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae phase variation pneumococcus Microbiology QR1-502 Melissa B. Oliver Ankita Basu Roy Ranjit Kumar Elliot J. Lefkowitz W. Edward Swords <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
description	ABSTRACT Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization, whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression. A panel of isogenic strains were created in the well-studied S. pneumoniae TIGR4 background that are “locked” in the transparent (n = 4) or opaque (n = 2) colony phenotype. The strains had significant differences in colony size which were stable over multiple passages in vitro and in vivo. While there were no significant differences in adherence for the phase-locked mutant strains to immortalized epithelial cells, biofilm formation and viability were reduced for the opaque variants in static assays. Nasopharyngeal colonization was stable for all strains, but the mortality rates differed between them. Transcript profiling by transcriptome sequencing (RNA-seq) analyses revealed that the expression levels of certain virulence factors were increased in a phase-specific manner. As epigenetic regulation of phase variation (often referred to as "phasevarion") is emerging as a common theme for mucosal pathogens, these results serve as a model for future studies of host-pathogen interactions. IMPORTANCE A growing number of bacterial species undergo epigenetic phase variation due to variable expression or specificity of DNA-modifying enzymes. For pneumococci, this phase variation has long been appreciated as being revealed by changes in colony opacity, which are reflected in changes in expression or accessibility of factors on the bacterial surface. Recent work showed that recombination-generated variation in alleles of the HsdS DNA methylase specificity subunit mediated pneumococcal phase variation. We generated phase-locked populations of S. pneumoniae TIGR4 expressing a single nonvariant hsdS allele and observed significant differences in gene expression and virulence. These results highlight the importance of focused pathogenesis studies within specific phase types. Moreover, the generation of single-allele hsdS constructs will greatly facilitate such studies.
format	article
author	Melissa B. Oliver Ankita Basu Roy Ranjit Kumar Elliot J. Lefkowitz W. Edward Swords
author_facet	Melissa B. Oliver Ankita Basu Roy Ranjit Kumar Elliot J. Lefkowitz W. Edward Swords
author_sort	Melissa B. Oliver
title	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
title_short	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
title_full	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
title_fullStr	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
title_full_unstemmed	<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes
title_sort	<named-content content-type="genus-species">streptococcus pneumoniae</named-content> tigr4 phase-locked opacity variants differ in virulence phenotypes
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/d7a553d2d0094ca295946d425fc9e4f5
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<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> TIGR4 Phase-Locked Opacity Variants Differ in Virulence Phenotypes

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