# Compound K14 inhibits bacterial killing and protease activity in Dictyostelium discoideum phagosomes

## TL;DR

A new compound, K14, inhibits bacterial destruction and protease activity in amoeba phagosomes, suggesting a role for proteases in immune defense.

## Contribution

Discovery of K14 as a novel inhibitor of phagosomal proteases and bacterial destruction in Dictyostelium.

## Key findings

- Compound K14 inhibits intracellular destruction of K. pneumoniae in D. discoideum.
- K14 reduces proteolytic activity in phagosomes, and this effect depends on Kil1.
- K14 reveals a previously unknown link between Kil1 and phagosomal proteases.

## Abstract

Phagocytic cells of the mammalian innate immune system play a critical role in protecting the body from bacterial infections. The multiple facets of this encounter (chemotaxis, phagocytosis, destruction, evasion and pathogenicity) are largely recapitulated in the phagocytic amoeba Dictyostelium discoideum. Here we identified a new chemical compound (K14; ZINC19168591) which inhibited intracellular destruction of ingested K. pneumoniae in D. discoideum cells. Concomitantly, K14 reduced proteolytic activity in D. discoideum phagosomes. In kil1 KO cells, K14 lost its ability to inhibit phagosomal proteolysis and to inhibit intra-phagosomal bacterial destruction, suggesting that K14 inhibits a Kil1-dependent protease involved in bacterial destruction. These observations stress the key role that proteases play in bacterial destruction. They also reveal an unsuspected link between Kil1 and phagosomal proteases. K14 can be used in the future as a tool to probe the role of different proteases in phagosomal physiology and in the destruction of ingested bacteria.