Specific host genes required for the killing of Klebsiella bacteria by phagocytes
Open accessAbstract
The amoeba Dictyostelium discoideum shares many traits with mammalian macrophages, in particular the ability to phagocytose and kill bacteria. In response, pathogenic bacteria use conserved mechanisms to fight amoebae and mammalian phagocytes. Here we developed an assay using Dictyostelium to monitor phagocyte-bacteria interactions. Genetic analysis revealed that the virulence of Klebsiella pneumoniae measured by this test is very similar to that observed in a mouse pneumonia model. Using this assay, two new host resistance genes (PHG1 and KIL1) were identified and shown to be involved in intracellular killing of K. pneumoniae by phagocytes. Phg1 is a member of the 9TM family of proteins, and Kil1 is a sulphotransferase. The loss of PHG1 resulted in Dictyostelium susceptibility to a small subset of bacterial species including K. pneumoniae. Remarkably, Drosophila mutants deficient for PHG1 also exhibited a specific susceptibility to K. pneumoniae infections. Systematic analysis of several additional Dictyostelium mutants created a two-dimensional virulence array, where the complex interactions between host and bacteria are visualized.
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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 [18]
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Nox enzymes and new thinking on reactive oxygen: A double-edged sword revisited
Lambeth, J. D., & Neish, A. S. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104651 · Cited by 495 · see citing works
The phagosome: compartment with a license to kill
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The origins of phagocytosis and eukaryogenesis
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“However, the level of conservation of phagosomal proteomes, as revealed by the comparison of the protein sets identified in the proteomic analyses, was surprisingly low: 118 proteins were detected in at least 3 of the 5 organisms for which proteomic analysis of phagosomes has been reported, of which 29 proteins were f…”
BackgroundGenome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium
Sillo, A., Bloomfield, G., Balest, A., Balbo, A., Pergolizzi, B., Peracino, B., Skelton, J., Ivens, A., & Bozzaro, S. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-291 · Cited by 69 · see citing works
- Authors
- Benghezal, M., Fauvarque, M.-O., Tournebize, R., Froquet, R., Marchetti, A., Bergeret, E., Lardy, B., Klein, G., Sansonetti, P., Charette, S. J., & Cosson, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Geneva (CH)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Institut Pasteur (FR)
- ORCID
- Venue
- Cellular Microbiology
- Publisher
- Hindawi Limited
- Published
- 2006-01
- Volume
- 8
- Issue
- 1
- Pages
- 139-148
- ISSN
- 1462-5814 (ISSN-L)
- 1462-5822
- OpenAlex
- W2000232525
- Cited by
- 136
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 5 · 2015: 1 · 2014: 9 · 2013: 12 · 2012: 4
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- Locations
- Cellular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Klebsiella pneumoniae, Dictyostelium discoideum, intracellular killing, host resistance genes, sulfotransferase, bacterial virulence, host-pathogen interaction, phagocytosis
- MeSH terms
- Animals, Cells, Cultured, Dictyostelium, Disease Models, Animal, Drosophila, Klebsiella pneumoniae, Membrane Proteins, Mutation, Phagocytosis, Virulence, Pneumonia, Bacterial, Mice
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