Population analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killing

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dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorWee, Bryan A.
dc.contributor.authorAlves, Joana
dc.contributor.authorLindsay, Diane, S.J.
dc.contributor.authorKlatt, Ann-Brit
dc.contributor.authorSargison, Fiona A.
dc.contributor.authorCameron, Ross L.
dc.contributor.authorPickering, Amy
dc.contributor.authorGorzynski, Jamie
dc.contributor.authorCorander, Jukka
dc.contributor.authorMarttinen, Pekka
dc.contributor.authorOpitz, Bastian
dc.contributor.authorSmith, Andrew J.
dc.contributor.authorFitzgerald, J. Ross
dc.contributor.departmentComputer Science Professors
dc.contributor.departmentDepartment of Computer Scienceen
dc.date.accessioned2021-12-31T13:55:43Z
dc.date.available2021-12-31T13:55:43Z
dc.date.issued2021-12-09
dc.description.abstractLegionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires’ disease. However, the microorganism is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 902 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We find that the capacity for human disease is representative of the breadth of species diversity although some clones are more commonly associated with clinical infections. We identified a single gene (lag-1) to be most strongly associated with clinical isolates. lag-1, which encodes an O-acetyltransferase for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. The gene confers resistance to complement-mediated killing in human serum by inhibiting deposition of classical pathway molecules on the bacterial surface. Furthermore, acquisition of lag-1 inhibits complement-dependent phagocytosis by human neutrophils, and promoted survival in a mouse model of pulmonary legionellosis. Thus, our results reveal L. pneumophila genetic traits linked to disease and provide a molecular basis for resistance to complement-mediated killing.en
dc.description.versionPeer revieweden
dc.format.extent13
dc.format.mimetypeapplication/pdf
dc.identifier.citationWee , B A , Alves , J , Lindsay , D S J , Klatt , A-B , Sargison , F A , Cameron , R L , Pickering , A , Gorzynski , J , Corander , J , Marttinen , P , Opitz , B , Smith , A J & Fitzgerald , J R 2021 , ' Population analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killing ' , Nature Communications , vol. 12 , no. 1 , 7165 . https://doi.org/10.1038/s41467-021-27478-zen
dc.identifier.doi10.1038/s41467-021-27478-z
dc.identifier.issn2041-1723
dc.identifier.otherPURE UUID: 2837673d-aac9-46ce-807a-9e3ba7d4dfda
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/2837673d-aac9-46ce-807a-9e3ba7d4dfda
dc.identifier.otherPURE LINK: https://www.nature.com/articles/s41467-021-27478-z
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/76913983/Population_analysis_of_Legionella_pneumophila_reveals_a_basis_for_resistance_to_complement_mediated_killing.pdf
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/111949
dc.identifier.urnURN:NBN:fi:aalto-2021123111089
dc.language.isoenen
dc.publisherNature Publishing Group
dc.relation.ispartofseriesNature Communicationsen
dc.relation.ispartofseriesVolume 12, issue 1en
dc.rightsopenAccessen
dc.titlePopulation analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killingen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionpublishedVersion
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