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

Wee, B. A. et al. (2021) Population analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killing. Nature Communications, 12, 7165. (doi: 10.1038/s41467-021-27478-z) (PMID:34887398) (PMCID:PMC8660822)

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Legionella 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.

Item Type:Articles
Additional Information:This work was supported by funding to JRF from the Chief Scientists Office Scotland (Grant No ETM/421), the Wellcome Trust Collaborative award (Grant No. 201531/Z/16/Z), the Medical Research Council (UK) award MR/N02995X/1, and Biotechnology and Biological Sciences Research Council institute strategic grant funding (ISP2) (Grant no. BB/P013740/1). Computing resources were supported in part by MRC CLIMB (Grant Number: MR/L015080/1). A.B.K. was supported by the International Max-Planck Research School (IMPRS-IDI), and B.O. by the German Research Foundation (OP 86/12-1 and SFB-TR84A1/A5).
Glasgow Author(s) Enlighten ID:Smith, Professor Andrew
Authors: Wee, 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., and Fitzgerald, J. R.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Nature Communications
Publisher:Nature Research
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Nature Communications 12: 7165
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173671Prof. R. Fitzgerald. Wellcome Trust Award 201531/Z/16/Z - Understanding bacterial host adaptation to combat infectious diseasesJose R PenadesWellcome Trust (WELLCOTR)R44516 - WT 201531/Z/16/ZInstitute of Infection, Immunity & Inflammation