<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>

ABSTRACT Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms o...

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Autores principales:	Laura A. Gonyar, Patrick E. Gelbach, Dennis G. McDuffie, Alexander F. Koeppel, Qing Chen, Gloria Lee, Louise M. Temple, Scott Stibitz, Erik L. Hewlett, Jason A. Papin, F. Heath Damron, Joshua C. Eby
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Bordetella Bordetella pertussis Tn-seq gene essentiality in vivo metabolism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d637cd0d98204829b52e75663e7cbc25
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spelling	oai:doaj.org-article:d637cd0d98204829b52e75663e7cbc252021-11-15T15:22:20Z<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>10.1128/mSphere.00694-182379-5042https://doaj.org/article/d637cd0d98204829b52e75663e7cbc252019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00694-18https://doaj.org/toc/2379-5042ABSTRACT Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous studies have provided insight into in vitro gene essentiality of this organism, very little is known about in vivo gene essentiality, a critical gap in knowledge, since B. pertussis has no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities of B. pertussis are especially tailored to the respiratory tract and that many of the genes involved in B. pertussis metabolism would be required to establish infection in vivo. In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentiality in vivo in a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesis in vivo. This is the first genome-wide evaluation of in vivo gene essentiality in B. pertussis and provides tools for future exploration. IMPORTANCE Our study describes the first in vivo transposon sequencing (Tn-seq) analysis of B. pertussis and identifies genes predicted to be essential for in vivo growth in a murine model of intranasal infection, generating key resources for future investigations into B. pertussis pathogenesis and vaccine design.Laura A. GonyarPatrick E. GelbachDennis G. McDuffieAlexander F. KoeppelQing ChenGloria LeeLouise M. TempleScott StibitzErik L. HewlettJason A. PapinF. Heath DamronJoshua C. EbyAmerican Society for MicrobiologyarticleBordetellaBordetella pertussisTn-seqgene essentialityin vivometabolismMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bordetella Bordetella pertussis Tn-seq gene essentiality in vivo metabolism Microbiology QR1-502
spellingShingle	Bordetella Bordetella pertussis Tn-seq gene essentiality in vivo metabolism Microbiology QR1-502 Laura A. Gonyar Patrick E. Gelbach Dennis G. McDuffie Alexander F. Koeppel Qing Chen Gloria Lee Louise M. Temple Scott Stibitz Erik L. Hewlett Jason A. Papin F. Heath Damron Joshua C. Eby <italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
description	ABSTRACT Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous studies have provided insight into in vitro gene essentiality of this organism, very little is known about in vivo gene essentiality, a critical gap in knowledge, since B. pertussis has no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities of B. pertussis are especially tailored to the respiratory tract and that many of the genes involved in B. pertussis metabolism would be required to establish infection in vivo. In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentiality in vivo in a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesis in vivo. This is the first genome-wide evaluation of in vivo gene essentiality in B. pertussis and provides tools for future exploration. IMPORTANCE Our study describes the first in vivo transposon sequencing (Tn-seq) analysis of B. pertussis and identifies genes predicted to be essential for in vivo growth in a murine model of intranasal infection, generating key resources for future investigations into B. pertussis pathogenesis and vaccine design.
format	article
author	Laura A. Gonyar Patrick E. Gelbach Dennis G. McDuffie Alexander F. Koeppel Qing Chen Gloria Lee Louise M. Temple Scott Stibitz Erik L. Hewlett Jason A. Papin F. Heath Damron Joshua C. Eby
author_facet	Laura A. Gonyar Patrick E. Gelbach Dennis G. McDuffie Alexander F. Koeppel Qing Chen Gloria Lee Louise M. Temple Scott Stibitz Erik L. Hewlett Jason A. Papin F. Heath Damron Joshua C. Eby
author_sort	Laura A. Gonyar
title	<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
title_short	<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
title_full	<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
title_fullStr	<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
title_full_unstemmed	<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>
title_sort	<italic toggle="yes">in vivo</italic> gene essentiality and metabolism in <named-content content-type="genus-species">bordetella pertussis</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/d637cd0d98204829b52e75663e7cbc25
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<italic toggle="yes">In Vivo</italic> Gene Essentiality and Metabolism in <named-content content-type="genus-species">Bordetella pertussis</named-content>

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