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Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation

Gori, A; Harrison, O; Mlia, E; Nishihara, Y; Chinkwita-Phiri, J; Mallewa, M; Dube, Q; ... Heyderman, R; + view all (2019) Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation. BioRxiv: Cold Spring Harbor, NY, USA. Green open access

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Abstract

Streptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised 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 co-morbidities. The genetic basis of GBS virulence and to what extent different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome wide association study approach to 1988 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 for 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, and suggest that human-associated GBS CCs have largely evolved in animal hosts before crossing to the humans and then spreading clonally.

Type: Working / discussion paper
Title: Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/574152
Publisher version: https://doi.org/10.1101/574152
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10088041
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