Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in people with cystic fibrosis (CF). Chronic P. aeruginosa isolates generally do not express O antigen and often have a mucoid phenotype, which is characterized by the overproduction of the exopolysaccha...

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Autores principales:	Ashley R. Cross, Joanna B. Goldberg
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Pseudomonas aeruginosa alginate lipopolysaccharide Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9d9122f982474e19ae52a78db2ce1830
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spelling	oai:doaj.org-article:9d9122f982474e19ae52a78db2ce18302021-11-15T15:55:14ZRemodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>10.1128/mBio.02914-182150-7511https://doaj.org/article/9d9122f982474e19ae52a78db2ce18302019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02914-18https://doaj.org/toc/2150-7511ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in people with cystic fibrosis (CF). Chronic P. aeruginosa isolates generally do not express O antigen and often have a mucoid phenotype, which is characterized by the overproduction of the exopolysaccharide alginate. Therefore, O antigen expression and the mucoid phenotype may be coordinately regulated upon chronic adaption to the CF lung. Here we demonstrate that PDO300, a mucoid strain derived from the nonmucoid laboratory isolate PAO1, does not produce very long O antigen due to decreased expression of Wzz2, the very long O antigen chain length control protein, and that mucoid clinical isolates express reduced levels of Wzz2 compared to nonmucoid isolates. Further, we show that forcing the expression of very long O antigen by PDO300, by providing wzz2 in trans, does not alter alginate production, suggesting that sugar precursors are not limited between the two biosynthesis pathways. Moreover, we confirm that AmrZ, a transcription factor highly expressed in mucoid strains, is a negative regulator of wzz2 promoter activity and very long O antigen expression. These experiments identify the first transcriptional regulator of O antigen chain length in P. aeruginosa and support a model where transition to a chronic mucoid phenotype is correlated with downregulation of very long O antigen through decreased Wzz2 production. IMPORTANCE Detection of mucoid Pseudomonas aeruginosa, characterized by the overproduction of alginate, is correlated with the establishment of a chronic pulmonary infection and disease progression in people with cystic fibrosis (CF). In addition to the overproduction of alginate, loss of O antigen lipopolysaccharide production is also selected for in chronic infection isolates. In this study, we have identified the regulatory network that inversely regulates O antigen and alginate production. Understanding the regulation of these chronic phenotypes will elucidate mechanisms that are important for the establishment of a long-term P. aeruginosa lung infection and ultimately provide an opportunity for intervention. Preventing P. aeruginosa from chronically adapting to the CF lung environment could provide a better outcome for people who are infected.Ashley R. CrossJoanna B. GoldbergAmerican Society for MicrobiologyarticlePseudomonas aeruginosaalginatelipopolysaccharideMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa alginate lipopolysaccharide Microbiology QR1-502
spellingShingle	Pseudomonas aeruginosa alginate lipopolysaccharide Microbiology QR1-502 Ashley R. Cross Joanna B. Goldberg Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
description	ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in people with cystic fibrosis (CF). Chronic P. aeruginosa isolates generally do not express O antigen and often have a mucoid phenotype, which is characterized by the overproduction of the exopolysaccharide alginate. Therefore, O antigen expression and the mucoid phenotype may be coordinately regulated upon chronic adaption to the CF lung. Here we demonstrate that PDO300, a mucoid strain derived from the nonmucoid laboratory isolate PAO1, does not produce very long O antigen due to decreased expression of Wzz2, the very long O antigen chain length control protein, and that mucoid clinical isolates express reduced levels of Wzz2 compared to nonmucoid isolates. Further, we show that forcing the expression of very long O antigen by PDO300, by providing wzz2 in trans, does not alter alginate production, suggesting that sugar precursors are not limited between the two biosynthesis pathways. Moreover, we confirm that AmrZ, a transcription factor highly expressed in mucoid strains, is a negative regulator of wzz2 promoter activity and very long O antigen expression. These experiments identify the first transcriptional regulator of O antigen chain length in P. aeruginosa and support a model where transition to a chronic mucoid phenotype is correlated with downregulation of very long O antigen through decreased Wzz2 production. IMPORTANCE Detection of mucoid Pseudomonas aeruginosa, characterized by the overproduction of alginate, is correlated with the establishment of a chronic pulmonary infection and disease progression in people with cystic fibrosis (CF). In addition to the overproduction of alginate, loss of O antigen lipopolysaccharide production is also selected for in chronic infection isolates. In this study, we have identified the regulatory network that inversely regulates O antigen and alginate production. Understanding the regulation of these chronic phenotypes will elucidate mechanisms that are important for the establishment of a long-term P. aeruginosa lung infection and ultimately provide an opportunity for intervention. Preventing P. aeruginosa from chronically adapting to the CF lung environment could provide a better outcome for people who are infected.
format	article
author	Ashley R. Cross Joanna B. Goldberg
author_facet	Ashley R. Cross Joanna B. Goldberg
author_sort	Ashley R. Cross
title	Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
title_short	Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
title_full	Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
title_fullStr	Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
title_full_unstemmed	Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>
title_sort	remodeling of o antigen in mucoid <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> via transcriptional repression of <italic toggle="yes">wzz2</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9d9122f982474e19ae52a78db2ce1830
work_keys_str_mv	AT ashleyrcross remodelingofoantigeninmucoidnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontentviatranscriptionalrepressionofitalictoggleyeswzz2italic AT joannabgoldberg remodelingofoantigeninmucoidnamedcontentcontenttypegenusspeciespseudomonasaeruginosanamedcontentviatranscriptionalrepressionofitalictoggleyeswzz2italic
_version_	1718427234052603904

Remodeling of O Antigen in Mucoid <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> via Transcriptional Repression of <italic toggle="yes">wzz2</italic>

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