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

Autor: Wee BA; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK., Alves J; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK., Lindsay DSJ; Bacterial Respiratory Infections Service (Ex Mycobacteria), Scottish Microbiology Reference Laboratory, Glasgow, Scotland, UK., Klatt AB; Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany., Sargison FA; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK., Cameron RL; NHS National Services Scotland, Health Protection Scotland, Glasgow, Scotland, UK., Pickering A; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK., Gorzynski J; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK., Corander J; Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.; Department of Biostatistics, University of Oslo, Oslo, Norway., Marttinen P; Helsinki Institute for Information Technology, Department of Computer Science, Aalto University, Aalto, Finland., Opitz B; Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany., Smith AJ; Bacterial Respiratory Infections Service (Ex Mycobacteria), Scottish Microbiology Reference Laboratory, Glasgow, Scotland, UK.; College of Medical, Veterinary & Life Sciences, Glasgow Dental Hospital & School, University of Glasgow, Glasgow, UK., Fitzgerald JR; The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, UK. Ross.Fitzgerald@ed.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Dec 09; Vol. 12 (1), pp. 7165. Date of Electronic Publication: 2021 Dec 09.
DOI: 10.1038/s41467-021-27478-z
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: