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Intracellular killing of bacteria: is Dictyostelium a model macrophage or an alien?

Cosson P, Lima WC - Cell. Microbiol. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Dpt for Cell Physiology and Metabolism, Centre Medical Universitaire, University of Geneva, 1 rue Michel Servet, 1211, Geneva 4, Switzerland.

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Molecular mechanisms involved in Dictyostelium sensing and killing of bacteria. Sensing of Klebsiella bacteria involves different players, notably FspA for bacteria-secreted folate, and a yet-unknown receptor of capsule components. TirA may also play a regulatory role in sensing. Mechanisms related to intracellular killing have been more extensively unravelled. Lysosomal activity (as denoted by the proteolytic efficiency inside the phagosome) and phagosomal biogenesis (including proper acidification and maturation) are major factors implicated in efficient killing. Proper regulation of adhesion and sulfation processes has also been implicated in successful killing.
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fig02: Molecular mechanisms involved in Dictyostelium sensing and killing of bacteria. Sensing of Klebsiella bacteria involves different players, notably FspA for bacteria-secreted folate, and a yet-unknown receptor of capsule components. TirA may also play a regulatory role in sensing. Mechanisms related to intracellular killing have been more extensively unravelled. Lysosomal activity (as denoted by the proteolytic efficiency inside the phagosome) and phagosomal biogenesis (including proper acidification and maturation) are major factors implicated in efficient killing. Proper regulation of adhesion and sulfation processes has also been implicated in successful killing.

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.


Intracellular killing of bacteria: is Dictyostelium a model macrophage or an alien?

Cosson P, Lima WC - Cell. Microbiol. (2014)

Molecular mechanisms involved in Dictyostelium sensing and killing of bacteria. Sensing of Klebsiella bacteria involves different players, notably FspA for bacteria-secreted folate, and a yet-unknown receptor of capsule components. TirA may also play a regulatory role in sensing. Mechanisms related to intracellular killing have been more extensively unravelled. Lysosomal activity (as denoted by the proteolytic efficiency inside the phagosome) and phagosomal biogenesis (including proper acidification and maturation) are major factors implicated in efficient killing. Proper regulation of adhesion and sulfation processes has also been implicated in successful killing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4291096&req=5

fig02: Molecular mechanisms involved in Dictyostelium sensing and killing of bacteria. Sensing of Klebsiella bacteria involves different players, notably FspA for bacteria-secreted folate, and a yet-unknown receptor of capsule components. TirA may also play a regulatory role in sensing. Mechanisms related to intracellular killing have been more extensively unravelled. Lysosomal activity (as denoted by the proteolytic efficiency inside the phagosome) and phagosomal biogenesis (including proper acidification and maturation) are major factors implicated in efficient killing. Proper regulation of adhesion and sulfation processes has also been implicated in successful killing.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Dpt for Cell Physiology and Metabolism, Centre Medical Universitaire, University of Geneva, 1 rue Michel Servet, 1211, Geneva 4, Switzerland.

Show MeSH
Related in: MedlinePlus