Intracellular killing of bacteria: is Dictyostelium a model macrophage or an alien?
Bottom Line: These results raise new questions on these processes, and challenge current models based largely on studies in mammalian phagocytes.In addition, recent studies suggest one additional level on complexity by revealing how Dictyostelium recognizes specifically various bacterial species and strains, and adapts its metabolism to process them.It remains to be seen to what extent mechanisms uncovered in Dictyostelium are also used in mammalian phagocytic cells.
Affiliation: Dpt for Cell Physiology and Metabolism, Centre Medical Universitaire, University of Geneva, 1 rue Michel Servet, 1211, Geneva 4, Switzerland.Show MeSH
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Mentions: Another way to test the depth of our knowledge of intracellular killing mechanisms, and to simultaneously test if functional redundancy prevents Dictyostelium mutants from exhibiting killing defects, is to isolate randomly killing-deficient mutants, and try to make sense of the gene products identified in this manner. The first killing-deficient mutant was identified serendipitously: phg1a KO cells, initially characterized as defective in adhesion to and ingestion of latex beads (Cornillon et al., 2000), were later found to also kill inefficiently ingested Klebsiella bacteria (Benghezal et al., 2006). This defect presumably accounts for the inability of phg1a KO cells to feed and grow upon Klebsiella bacteria. In the same study, Kil1 was identified as a high-copy suppressor of the killing defect phg1a KO cells, and kil1 KO cells were shown to kill inefficiently Klebsiella bacteria. The role of Phg1a in intracellular killing is probably due to the fact that it controls intracellular transport and stability of membrane proteins (Froquet et al., 2012), and that in its absence the Kil1 protein is unstable and virtually depleted from cells (Le Coadic et al., 2013) (Fig. 2 ). Kil1 is a sulfotransferase, and no direct link has previously been established between sulfation of host proteins and host–pathogen interactions in metazoans. Sulfation has been described to play a role in receptor–ligand interactions (Hemmerich and Rosen, 2000; Park et al., 2010), but its role in intracellular killing remains to be determined.
Affiliation: Dpt for Cell Physiology and Metabolism, Centre Medical Universitaire, University of Geneva, 1 rue Michel Servet, 1211, Geneva 4, Switzerland.