Abstract

Intracellular killing is a complex process by which phagocytic cells eliminate microorganisms, once engulfed. In human tissues, intracellular killing is vital to fight off invading pathogens such as Klebsiella pneumoniae or for tissue homeostasis. Intracellular killing is mainly carried out within macrophages and neutrophils. Using Dictyostelium discoideum as a model organism for macrophages enables us to perform large scale random mutagenesis screen to find genes involved in intracellular killing of K. pneumoniae. Two of them have already been described: kil1 and kil2. Kil1 is a sulphotransferase and Kil2 a phagosomal magnesium pump. We characterized two new genes involved in intracellular killing: vps13F and lrrkA. Vps13F is most likely involved in trafficking IC killing effectors to the phagosomes and LrrkA is at the convergence between sensing bacterial cue (i.e. folate) and activating intracellular killing mechanisms by respectively enhancing motility when folate is present and regulating Kil2 activity during the phagosome maturation.

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