Compound K14 inhibits bacterial killing and protease activity in <i>Dictyostelium discoideum</i> phagosomes

Article Article scientifique Article Compound K14 inhibits bacterial killing and protease activity in <i>Dictyostelium discoideum</i> phagosomes eng 2024-08-26 author Ifrid Estelle Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 854662 author Ouertatani Hajer Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 734371 author Zein El Dine Hiba Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 403837 Département de physiologie cellulaire et métabolisme (PHYME) author Jauslin Tania Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 850400 Structure enseignement (ENSI) author Chiriano Gianpaolo Pharmaceutical biochemistry, School of pharmaceutical sciences, University of Geneva, Geneva, Switzerland. 784524 author Scapozza Leonardo 0000-0003-1079-648X Pharmaceutical biochemistry, School of pharmaceutical sciences, University of Geneva, Geneva, Switzerland. 600318 Section des sciences pharmaceutiques (FARMA) author Lamrabet Otmane 0000-0002-7015-1942 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 862612 author Cosson Pierre 0000-0002-4881-0358 Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 119596 Département de physiologie cellulaire et métabolisme (PHYME) e0309327 10.1371/journal.pone.0309327 39186559 1932-6203 PMC11346726 https://dx.plos.org/10.1371/journal.pone.0309327 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. Dictyostelium / enzymology Peptide Hydrolases / metabolism Phagocytosis / drug effects Phagosomes / metabolism Proteolysis / drug effects Protozoan Proteins / genetics Protozoan Proteins / metabolism Dewey 612 Dewey 615 Swiss National Science Foundation Killing of bacteria in phagosomes: biochemistry, genetics and specificity. 201186 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C 31 Section des sciences pharmaceutiques 17 false 111 Phagocytose 140 880 Biochimie pharmaceutique https://doi.org/10.26037/yareta:gcr2sjjs5zcnzosxzuticrtuyy PloS one 19 8 e4f22010-7c34-4458-82fb-836d6462af16 Article (Published version) Public pone.0309327.pdf 2122811 application/pdf CC BY-4.0 f3c75be38b9cf644468b40d31a766e2a487509b094064543e26f4df776851ab8 5c44d10f-eb0e-4f50-8c99-e4e8e4f248d6 Supplemental data Public pone.0309327.s001.pdf 869852 application/pdf ae6d6786c8a208d1f3ae5a757c1d25f01a40c95dbbd163b34079cd61ed198e2f openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté des sciences / Section des sciences pharmaceutiques

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Compound K14 inhibits bacterial killing and protease activity in Dictyostelium discoideum phagosomes	PloS one			2024	59	189

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