PilY1 PromotesLegionella pneumophilaInfection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility.
Legionnaires' disease is an acute fibrinopurulent pneumonia. During infectionLegionella pneumophilaadheres to the alveolar lining and replicates intracellularly within recruited macrophages. Here we provide a sequence and domain composition analysis of theL. pneumophilaPilY1 protein, which has a high homology to PilY1 ofPseudomonas aeruginosa. PilY1 proteins of both pathogens contain a von Willebrand factor A (vWFa) and a C-terminal PilY domain. Using cellular fractionation, we assigned theL. pneumophilaPilY1 as an outer membrane protein that is only expressed during the transmissive stationary growth phase. PilY1 contributes to infection of human lung tissue explants (HLTEs). A detailed analysis using THP-1 macrophages and A549 lung epithelial cells revealed that this contribution is due to multiple effects depending on host cell type. Deletion of PilY1 resulted in a lower replication rate in THP-1 macrophages but not in A549 cells. Further on, adhesion to THP-1 macrophages and A549 epithelial cells was decreased. Additionally, the invasion into non-phagocytic A549 epithelial cells was drastically reduced when PilY1 was absent. Complementation variants of a PilY1-negative mutant revealed that the C-terminal PilY domain is essential for restoring the wild type phenotype in adhesion, while the putatively mechanosensitive vWFa domain facilitates invasion into non-phagocytic cells. Since PilY1 also promotes twitching motility ofL. pneumophila, we discuss the putative contribution of this newly described virulence factor for bacterial dissemination within infected lung tissue.
Institut für Mikrobiologie, Technische Universität Braunschweig Braunschweig, Germany.
Julia
J
Hoppe
Institut für Mikrobiologie, Technische Universität Braunschweig Braunschweig, Germany.
Can M
CM
Ünal
Institut für Mikrobiologie, Technische Universität Braunschweig Braunschweig, Germany.
Stefanie
S
Thiem
Institut für Mikrobiologie, Technische Universität Braunschweig Braunschweig, Germany.
Louisa
L
Grimpe
Pathology of the University Hospital of Lübeck and the Leibniz Research CenterBorstel, Germany; Airway Research Center North (ARCN), Member of the German Center for Lung ResearchBorstel, Germany.
Torsten
T
Goldmann
Institut für Pathologie, Klinikum Braunschweig Braunschweig, Germany.
Nikolaus
N
Gaßler
Klinikum Salzdahlumerstraße Braunschweig Braunschweig, Germany.
Matthias
M
Richter
Center for Proteomics, University of Rijeka Rijeka, Croatia.
Olga
O
Shevchuk
Institut für Mikrobiologie, Technische Universität BraunschweigBraunschweig, Germany; Helmholtz Center for Infection ResearchBraunschweig, Germany.
Michael
M
Steinert
D001422:Bacterial Adhesion / Q000235:genetics*; D036781:Fimbriae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D007877:Legionnaires' Disease / Q000382:microbiology* / Q000473:pathology; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D009154:Mutation; D000072417:Protein Domains; D021381:Protein Transport; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D037521:Virulence Factors; D036781:Fimbriae Proteins
L. pneumophila; PilY1; adherence; human lung tissue explants; invasion; twitching motility