Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens

ABSTRACT O-antigens are glycopolymers in lipopolysaccharides expressed on the cell surface of Gram-negative bacteria. Variability in the O-antigen structure constitutes the basis for the establishment of the serotyping schema. We pursued a two-pronged approach to define the basis for O-antigen struc...

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Autores principales:	Yara Seif, Jonathan M. Monk, Henrique Machado, Erol Kavvas, Bernhard O. Palsson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Salmonella genome analysis metabolism serogroups Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d97cc710344d453db7df1c5d95c4ab63
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spelling	oai:doaj.org-article:d97cc710344d453db7df1c5d95c4ab632021-11-15T16:22:09ZSystems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens10.1128/mBio.01247-192150-7511https://doaj.org/article/d97cc710344d453db7df1c5d95c4ab632019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01247-19https://doaj.org/toc/2150-7511ABSTRACT O-antigens are glycopolymers in lipopolysaccharides expressed on the cell surface of Gram-negative bacteria. Variability in the O-antigen structure constitutes the basis for the establishment of the serotyping schema. We pursued a two-pronged approach to define the basis for O-antigen structural diversity. First, we developed a bottom-up systems biology approach to O-antigen metabolism by building a reconstruction of Salmonella O-antigen biosynthesis and used it to (i) update 410 existing Salmonella strain-specific metabolic models, (ii) predict a strain’s serogroup and its O-antigen glycan synthesis capability (yielding 98% agreement with experimental data), and (iii) extend our workflow to more than 1,400 Gram-negative strains. Second, we used a top-down pangenome analysis to elucidate the genetic basis for intraserogroup O-antigen structural variations. We assembled a database of O-antigen gene islands from over 11,000 sequenced Salmonella strains, revealing (i) that gene duplication, pseudogene formation, gene deletion, and bacteriophage insertion elements occur ubiquitously across serogroups; (ii) novel serotypes in the group O:4 B2 variant, as well as an additional genotype variant for group O:4, and (iii) two novel O-antigen gene islands in understudied subspecies. We thus comprehensively defined the genetic basis for O-antigen diversity. IMPORTANCE Lipopolysaccharides are a major component of the outer membrane in Gram-negative bacteria. They are composed of a conserved lipid structure that is embedded in the outer leaflet of the outer membrane and a polysaccharide known as the O-antigen. O-antigens are highly variable in structure across strains of a species and are crucial to a bacterium’s interactions with its environment. They constitute the first line of defense against both the immune system and bacteriophage infections and have been shown to mediate antimicrobial resistance. The significance of our research is in identifying the metabolic and genetic differences within and across O-antigen groups in Salmonella strains. Our effort constitutes a first step toward characterizing the O-antigen metabolic network across Gram-negative organisms and a comprehensive overview of genetic variations in Salmonella.Yara SeifJonathan M. MonkHenrique MachadoErol KavvasBernhard O. PalssonAmerican Society for MicrobiologyarticleSalmonellagenome analysismetabolismserogroupsMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Salmonella genome analysis metabolism serogroups Microbiology QR1-502
spellingShingle	Salmonella genome analysis metabolism serogroups Microbiology QR1-502 Yara Seif Jonathan M. Monk Henrique Machado Erol Kavvas Bernhard O. Palsson Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
description	ABSTRACT O-antigens are glycopolymers in lipopolysaccharides expressed on the cell surface of Gram-negative bacteria. Variability in the O-antigen structure constitutes the basis for the establishment of the serotyping schema. We pursued a two-pronged approach to define the basis for O-antigen structural diversity. First, we developed a bottom-up systems biology approach to O-antigen metabolism by building a reconstruction of Salmonella O-antigen biosynthesis and used it to (i) update 410 existing Salmonella strain-specific metabolic models, (ii) predict a strain’s serogroup and its O-antigen glycan synthesis capability (yielding 98% agreement with experimental data), and (iii) extend our workflow to more than 1,400 Gram-negative strains. Second, we used a top-down pangenome analysis to elucidate the genetic basis for intraserogroup O-antigen structural variations. We assembled a database of O-antigen gene islands from over 11,000 sequenced Salmonella strains, revealing (i) that gene duplication, pseudogene formation, gene deletion, and bacteriophage insertion elements occur ubiquitously across serogroups; (ii) novel serotypes in the group O:4 B2 variant, as well as an additional genotype variant for group O:4, and (iii) two novel O-antigen gene islands in understudied subspecies. We thus comprehensively defined the genetic basis for O-antigen diversity. IMPORTANCE Lipopolysaccharides are a major component of the outer membrane in Gram-negative bacteria. They are composed of a conserved lipid structure that is embedded in the outer leaflet of the outer membrane and a polysaccharide known as the O-antigen. O-antigens are highly variable in structure across strains of a species and are crucial to a bacterium’s interactions with its environment. They constitute the first line of defense against both the immune system and bacteriophage infections and have been shown to mediate antimicrobial resistance. The significance of our research is in identifying the metabolic and genetic differences within and across O-antigen groups in Salmonella strains. Our effort constitutes a first step toward characterizing the O-antigen metabolic network across Gram-negative organisms and a comprehensive overview of genetic variations in Salmonella.
format	article
author	Yara Seif Jonathan M. Monk Henrique Machado Erol Kavvas Bernhard O. Palsson
author_facet	Yara Seif Jonathan M. Monk Henrique Machado Erol Kavvas Bernhard O. Palsson
author_sort	Yara Seif
title	Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
title_short	Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
title_full	Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
title_fullStr	Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
title_full_unstemmed	Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens
title_sort	systems biology and pangenome of <italic toggle="yes">salmonella</italic> o-antigens
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/d97cc710344d453db7df1c5d95c4ab63
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Systems Biology and Pangenome of <italic toggle="yes">Salmonella</italic> O-Antigens

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