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The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum
Open accessAbstract
Genetically accessible host models are useful for studying microbial pathogenesis because they offer the means to identify novel strategies that pathogens use to evade immune mechanisms, cause cellular injury, and induce disease. We have developed conditions under which the human pathogen Pseudomonas aeruginosa infects Dictyostelium discoideum , a genetically tractable eukaryotic organism. When D. discoideum is plated on nutrient agar plates with different P. aeruginosa strains, the bacteria form lawns on these plates with amoebae embedded in them. Virulent P. aeruginosa strains kill these amoebae and leave an intact bacterial lawn. A number of P. aeruginosa mutants have been identified that are avirulent in this assay. Amoebae feed on these bacteria and form plaques in their bacterial lawns. One avirulent mutant strain carries an insertional mutation in the lasR gene. LasR is a transcription factor that controls a number of virulence genes in a density-dependent fashion. Another class of avirulent P. aeruginosa mutants is defective in type III secretion. One mutant lacks the PscJ protein, a structural component of the secretion apparatus, suggesting that cytotoxins are injected into the D. discoideum cell. One of these cytotoxins is ExoU, and exoU mutants are avirulent toward D. discoideum . Complementation of the lasR and exoU mutations restores virulence. Therefore, P. aeruginosa uses conserved virulence pathways to kill D. discoideum .
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“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 [13]
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Metadata
- Authors
- Pukatzki, S., Kessin, R. H., & Mekalanos, J. J.
- Affiliations
- Harvard University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-02-26
- Volume
- 99
- Issue
- 5
- Pages
- 3159-3164
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122489
- OpenAlex
- W2104817697
- Cited by
- 289
- References
- 42
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 16 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 18 · 2013: 13 · 2012: 14
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cystic Fibrosis Foundation
- National Institutes of Health
- University of California, San Francisco
- National Institute of General Medical Sciences (R01GM033136, GM33136-20)
- National Institute of Allergy and Infectious Diseases (R01AI026289, AI-26289)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Keywords
- Pseudomonas aeruginosa, Dictyostelium discoideum, bacterial pathogenesis, virulence factors, type III secretion system, avirulent mutants, host-pathogen interaction, density dependence
- MeSH terms
- Animals, Bacterial Proteins, Bacterial Toxins, Cytotoxins, Dictyostelium, DNA-Binding Proteins, Humans, Phagocytosis, Pseudomonas aeruginosa, Soil Microbiology, Virulence, Trans-Activators
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