Open AccessVps13F links bacterial recognition and intracellular killing in Dictyostelium
Author(s) -
Leiba Jade,
Sabra Ayman,
Bodinier Romain,
Marchetti Anna,
Lima Wanessa C.,
Melotti Astrid,
Perrin Jackie,
Burdet Frederic,
Pagni Marco,
Soldati Thierry,
Lelong Emmanuelle,
Cosson Pierre
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12722
Subject(s) - intracellular , biology , intracellular parasite , dictyostelium discoideum , dictyostelium , microbiology and biotechnology , endocytic cycle , cell , gene , endocytosis , genetics
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 .