title: Vps13F links bacterial recognition and intracellular killing in Dictyostelium.
abstract: Bacterial sensing, ingestion, and killing by phagocytic cells are essential processes to protect the human body from infectious microorganisms. The cellular mechanisms involved in intracellular killing, their relative importance, and their specificity towards different bacteria are however poorly defined. In this study, we used Dictyostelium discoideum, a phagocytic cell model amenable to genetic analysis, to identify new gene products involved in intracellular killing. A random genetic screen led us to identify the role of Vps13F in intracellular killing of Klebsiella pneumoniae. Vps13F knock-out (KO) cells exhibited a delayed intracellular killing of K. pneumoniae, although the general organization of the phagocytic and endocytic pathway appeared largely unaffected. Transcriptomic analysis revealed that vps13F KO cells may be functionally similar to previously characterized fspA KO cells, shown to be defective in folate sensing. Indeed, vps13F KO cells showed a decreased chemokinetic response to various stimulants, suggesting a direct or indirect role of Vps13F in intracellular signaling. Overstimulation with excess folate restored efficient killing in vps13F KO cells. Finally, genetic inactivation of Far1, the folate receptor, resulted in inefficient intracellular killing of K. pneumoniae. Together, these observations show that stimulation of Dictyostelium by bacterial folate is necessary for rapid intracellular killing of K. pneumoniae.
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jade
authors.identifier: 0000-0001-8751-1169
authors.initials: J
authors.lastname: Leiba
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Ayman
authors.initials: A
authors.lastname: Sabra
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Romain
authors.initials: R
authors.lastname: Bodinier
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Marchetti
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Wanessa C
authors.initials: WC
authors.lastname: Lima
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Melotti
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jackie
authors.initials: J
authors.lastname: Perrin
authors.affiliation: Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Burdet
authors.affiliation: Vital-IT, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Pagni
authors.affiliation: Department of Biochemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Thierry
authors.identifier: 0000-0002-2056-7931
authors.initials: T
authors.lastname: Soldati
authors.affiliation: Genomic Research Laboratory, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lelong
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
mesh_terms: D004023:Dictyostelium / Q000382:microbiology* / Q000502:physiology*; D058975:Folate Receptor 1 / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D055786:Gene Knockout Techniques; D007711:Klebsiella pneumoniae / Q000502:physiology*; D010587:Phagocytosis / Q000235:genetics* / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics
chemical_list: D058975:Folate Receptor 1; D015800:Protozoan Proteins; D033921:Vesicular Transport Proteins; D005492:Folic Acid