PUBLICATION
Dissection of Francisella-Host Cell Interactions in Dictyostelium discoideum
- Authors
- Lampe, E.O., Brenz, Y., Herrmann, L., Repnik, U., Griffiths, G., Zingmark, C., Sjöstedt, A., Winther-Larsen, H.C., Hagedorn, M.
- ID
- ZDB-PUB-151230-8
- Date
- 2015
- Source
- Applied and environmental microbiology 82(5): 1586-98 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Cytosol/microbiology
- Dictyostelium/microbiology*
- Endosomes/microbiology
- Francisella/growth & development*
- Host-Pathogen Interactions*
- Models, Biological*
- Phagocytosis
- PubMed
- 26712555 Full text @ Appl. Environ. Microbiol.
Citation
Lampe, E.O., Brenz, Y., Herrmann, L., Repnik, U., Griffiths, G., Zingmark, C., Sjöstedt, A., Winther-Larsen, H.C., Hagedorn, M. (2015) Dissection of Francisella-Host Cell Interactions in Dictyostelium discoideum. Applied and environmental microbiology. 82(5):1586-98.
Abstract
Francisella bacteria cause severe disease in both vertebrates and invertebrates and include one of the most infectious human pathogens. Mammalian cell lines have mainly been used to study the mechanisms by which Francisella manipulates its host to replicate within a large variety of hosts and cell types, including macrophages. Here, we describe the establishment of a genetically and biochemically tractable infection model: the amoeba Dictyostelium discoideum combined with the fish pathogen F. noatunensis subsp noatunensis (F.n.n.). Phagocytosed F.n.n. interact with the endosomal pathway and escape further phagosomal maturation by translocating into the host cell cytosol. F.n.n. lacking IglC, a known virulence determinant required for Francisella intracellular replication, follows the normal phagosomal maturation and does not grow in Dictyostelium. The attenuation of the F.n.n. ΔiglC mutant was confirmed in a zebrafish embryo model, where growth of F.n.n. ΔiglC was restricted. In Dictyostelium, F.n.n. interacts with the autophagic machinery. The intracellular bacteria colocalize with autophagic markers and when autophagy is impaired (Dictyostelium Δatg1) F.n.n. accumulate within Dictyostelium cells. Taken together, the Dictyostelium-F.n.n. infection model recapitulates the course of infection described in other host systems. The genetic and biochemical tractability of this system allows new approaches to elucidate the dynamic interactions between pathogenic Francisella and its host organism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping