Calnexin, calreticulin and cytoskeleton-associated proteins modulate uptake and growth of Legionella pneumophila in Dictyostelium discoideum
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The haploid amoeba Dictyostelium discoideum is a versatile host system for studying cellular aspects of Legionella pathogenicity. Previous studies have shown that the internalization of L. pneumophila leads to an endoplasmic reticulum (ER)-derived organelle that supports intracellular replication of the bacteria. In this study a roadmap of host-cell factors involved in this process was developed. Phagocytosis assays with specific cellular inhibitors and the effects of well defined host-cell mutants revealed that cytoplasmic calcium levels, cytoskeleton-associated proteins and the calcium-binding proteins of the ER, calreticulin and calnexin, specifically influence the uptake and intracellular growth of L. pneumophila. Confocal microscopic time series with green fluorescent protein (GFP)-tagged calnexin and calreticulin demonstrated the accumulation of both proteins in the phagocytic cup of L. pneumophila-infected host cells. In contrast to the control experiment with Escherichia coli-containing phagosomes, both proteins decorated the replicative vacuole of L. pneumophila during the entire growth phase of the bacteria. The cumulative effects of cytosolic calcium levels, the spatial distribution of calnexin and calreticulin, and the defective invasion and replication of L. pneumophila in calnexin- and calreticulin-minus cells suggest that these factors are part of a regulatory system that leads to the specific vacuole of L. pneumophila.
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Several bacterial pathogens for humans, such as legionella, mycobacteria and salmonella, are pathogenic also for Dictyostelium.
“Several bacterial pathogens for humans, such as legionella, mycobacteria and salmonella, are pathogenic also for Dictyostelium, favouring the use of this model to study host-pathogen interactions [9-19].”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [14]
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- Authors
- Fajardo, M., Schleicher, M., Noegel, A., Bozzaro, S., Killinger, S., Heuner, K., Hacker, J., & Steinert, M.
- Affiliations
- University of Würzburg (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of Cologne (DE)
- Ospedale San Luigi Gonzaga (IT)
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 2004-09-01
- Volume
- 150
- Issue
- 9
- Pages
- 2825-2835
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- OpenAlex
- W2155429253
- Cited by
- 73
- References
- 54
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 413)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Legionella pneumophila, Dictyostelium discoideum, calnexin, calreticulin, cytoskeleton-associated proteins, phagocytosis, bacterial internalization, intracellular replication, intracellular calcium, host-pathogen interaction, phagosome
- MeSH terms
- Animals, Calcium, Calcium-Binding Proteins, Cytoplasm, Cytoskeleton, Dictyostelium, Mutation, Phagocytosis, Recombinant Fusion Proteins, Vacuoles, Colony Count, Microbial, Protozoan Proteins, Legionella pneumophila, Gene Deletion, Genes, Reporter, Microscopy, Confocal, Artificial Gene Fusion, Calnexin, Calreticulin
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