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

Autor: Ifrid E; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Ouertatani-Sakouhi H; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Zein El Dine H; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Jauslin T; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Chiriano G; Pharmaceutical biochemistry, School of pharmaceutical sciences, University of Geneva, Geneva, Switzerland., Scapozza L; Pharmaceutical biochemistry, School of pharmaceutical sciences, University of Geneva, Geneva, Switzerland., Lamrabet O; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Cosson P; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 26; Vol. 19 (8), pp. e0309327. Date of Electronic Publication: 2024 Aug 26 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0309327
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ifrid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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