title: Candida albicans actively modulates intracellular membrane trafficking in mouse macrophage phagosomes.
abstract: The intracellular trafficking/survival strategies of the opportunistic human pathogen Candida albicans are poorly understood. Here we investigated the infection of RAW264.7 macrophages with a virulent wild-type (WT) filamentous C. albicans strain and a hyphal signalling-defective mutant (efg1Delta/cph1Delta). A comparative analysis of the acquisition by phagosomes of actin, and of early/late endocytic organelles markers of the different fungal strains was performed and related to Candida's survival inside macrophages. Our results show that both fungal strains have evolved a similar mechanism to subvert the 'lysosomal' system, as seen by the inhibition of the phagosome fusion with compartments enriched in the lysobisphosphatidic acid and the vATPase, and thereby the acquisition of a low pH from the outset of infection. Besides, the virulent WT strain displayed additional specific survival strategies to prevent its targeting to compartmentsdisplaying late endosomal/lysosomal features, such as induction of active recycling out of phagosomes of the lysosomal membrane protein LAMP-1, the lysosomal protease cathepsin D and preinternalized colloidal gold. Finally, both virulent and efg1Delta/cph1Delta mutant fungal strains actively suppressed the production of macrophage nitric oxide (NO), although their cell wall extracts were potent inducers of NO.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense, 28040-Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Fernández-Arenas
authors.forename: Christopher K E
authors.initials: CK
authors.lastname: Bleck
authors.forename: César
authors.initials: C
authors.lastname: Nombela
authors.forename: Concha
authors.initials: C
authors.lastname: Gil
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Rosalía
authors.initials: R
authors.lastname: Diez-Orejas
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D002402:Cathepsin D / Q000378:metabolism; D002460:Cell Line; D017979:Gold Colloid / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism* / Q000382:microbiology / Q000502:physiology; D014774:Virulence / Q000235:genetics; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002402:Cathepsin D; D017979:Gold Colloid; D051907:Lysosomal Membrane Proteins; D009569:Nitric Oxide; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1