Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation

ABSTRACT Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for e...

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Autores principales:	Andrea Gori, Odile B. Harrison, Ethwako Mlia, Yo Nishihara, Jia Mun Chan, Jacquline Msefula, Macpherson Mallewa, Queen Dube, Todd D. Swarthout, Angela H. Nobbs, Martin C. J. Maiden, Neil French, Robert S. Heyderman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Streptococcus agalactiae pan-genome GWAS population structure bacterial phylogeny virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/993fbc4e328d4f2eadcd44b11a7cd9b1
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spelling	oai:doaj.org-article:993fbc4e328d4f2eadcd44b11a7cd9b12021-11-15T15:56:47ZPan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation10.1128/mBio.00728-202150-7511https://doaj.org/article/993fbc4e328d4f2eadcd44b11a7cd9b12020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00728-20https://doaj.org/toc/2150-7511ABSTRACT Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities. The genetic basis of GBS virulence and the extent to which different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome-wide association study (GWAS) approach to 1,988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism, and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23, for example, we have identified genes encoding pilus, quorum-sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence. IMPORTANCE GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease. The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host. These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted.Andrea GoriOdile B. HarrisonEthwako MliaYo NishiharaJia Mun ChanJacquline MsefulaMacpherson MallewaQueen DubeTodd D. SwarthoutAngela H. NobbsMartin C. J. MaidenNeil FrenchRobert S. HeydermanAmerican Society for MicrobiologyarticleStreptococcus agalactiaepan-genomeGWASpopulation structurebacterial phylogenyvirulenceMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus agalactiae pan-genome GWAS population structure bacterial phylogeny virulence Microbiology QR1-502
spellingShingle	Streptococcus agalactiae pan-genome GWAS population structure bacterial phylogeny virulence Microbiology QR1-502 Andrea Gori Odile B. Harrison Ethwako Mlia Yo Nishihara Jia Mun Chan Jacquline Msefula Macpherson Mallewa Queen Dube Todd D. Swarthout Angela H. Nobbs Martin C. J. Maiden Neil French Robert S. Heyderman Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
description	ABSTRACT Streptococcus agalactiae (group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities. The genetic basis of GBS virulence and the extent to which different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome-wide association study (GWAS) approach to 1,988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism, and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23, for example, we have identified genes encoding pilus, quorum-sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence. IMPORTANCE GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease. The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host. These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted.
format	article
author	Andrea Gori Odile B. Harrison Ethwako Mlia Yo Nishihara Jia Mun Chan Jacquline Msefula Macpherson Mallewa Queen Dube Todd D. Swarthout Angela H. Nobbs Martin C. J. Maiden Neil French Robert S. Heyderman
author_facet	Andrea Gori Odile B. Harrison Ethwako Mlia Yo Nishihara Jia Mun Chan Jacquline Msefula Macpherson Mallewa Queen Dube Todd D. Swarthout Angela H. Nobbs Martin C. J. Maiden Neil French Robert S. Heyderman
author_sort	Andrea Gori
title	Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
title_short	Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
title_full	Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
title_fullStr	Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
title_full_unstemmed	Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation
title_sort	pan-gwas of <named-content content-type="genus-species">streptococcus agalactiae</named-content> highlights lineage-specific genes associated with virulence and niche adaptation
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/993fbc4e328d4f2eadcd44b11a7cd9b1
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Pan-GWAS of <named-content content-type="genus-species">Streptococcus agalactiae</named-content> Highlights Lineage-Specific Genes Associated with Virulence and Niche Adaptation

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