Vps13F links bacterial recognition and intracellular killing in Dictyostelium

Leiba, Jade; Sabra, Ayman; Bodinier, Romain; Marchetti, Anna; Lima, Wanessa C; Melotti, Astrid; Perrin Simonnot, Jackie; Burdet, Frederic; Pagni, Marco; Soldati, Thierry; Lelong-Favre Alborini, Emmanuelle; Cosson, Pierre

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Title		Vps13F links bacterial recognition and intracellular killing in Dictyostelium
Authors		Leiba, Jade Sabra, Ayman Bodinier, Romain Marchetti, Anna Lima, Wanessa C Melotti, Astrid Perrin Simonnot, Jackie Burdet, Frederic Pagni, Marco Soldati, Thierry Lelong-Favre Alborini, Emmanuelle Cosson, Pierre show all authors [1 - 12]
Published in		Cellular Microbiology. 2017
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 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.
Identifiers		DOI: 10.1111/cmi.12722 PMID: 28076662
Full text		Article (Published version) (898 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté des sciences / Section de chimie et biochimie / Département de biochimie
Research group		Groupe Soldati
Citation (ISO format)		LEIBA, Jade et al. Vps13F links bacterial recognition and intracellular killing in Dictyostelium. In: Cellular Microbiology, 2017. https://archive-ouverte.unige.ch/unige:92039