title: Role of Arf GTPases in fungal morphogenesis and virulence.
abstract: Virulence of the human fungal pathogen Candida albicans depends on the switch from budding to filamentous growth, which requires sustained membrane traffic and polarized growth. In many organisms, small GTPases of the Arf (ADP-ribosylation factor) family regulate membrane/protein trafficking, yet little is known about their role in fungal filamentous growth. To investigate these GTPases in C. albicans, we generated loss of function mutants in all 3 Arf proteins, Arf1-Arf3, and 2 Arf-like proteins, Arl1 and Arl3. Our results indicate that of these proteins, Arf2 is required for viability and sensitivity to antifungal drugs. Repressible ARF2 expression results in defects in filamentous growth, cell wall integrity and virulence, likely due to alteration of the Golgi. Arl1 is also required for invasive filamentous growth and, although arl1/arl1 cells can initiate hyphal growth, hyphae are substantially shorter than that of the wild-type, due to the inability of this mutant to maintain hyphal growth at a single site. We show that this defect does not result from an alteration of phospholipid distribution and is unlikely to result from the sole Golgin Imh1 mislocalization, as Imh1 is not required for invasive filamentous growth. Rather, our results suggest that the arl1/arl1 hyphal growth defect results from increased secretion in this mutant. Strikingly, the arl1/arl1 mutant is drastically reduced in virulence during oropharyngeal candidiasis. Together, our results highlight the importance of Arl1 and Arf2 as key regulators of hyphal growth and virulence in C. albicans and identify a unique function of Arl1 in secretion.
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Parc Valrose, Nice, France.
authors.forename: Hayet
authors.initials: H
authors.lastname: Labbaoui
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Parc Valrose, Nice, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bogliolo
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Parc Valrose, Nice, France.
authors.forename: Vikram
authors.initials: V
authors.lastname: Ghugtyal
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
authors.forename: Norma V
authors.initials: NV
authors.lastname: Solis
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
authors.forename: Scott G
authors.identifier: 0000-0001-7278-3700
authors.initials: SG
authors.lastname: Filler
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Parc Valrose, Nice, France.
authors.forename: Robert A
authors.identifier: 0000-0002-5216-5013
authors.initials: RA
authors.lastname: Arkowitz
authors.affiliation: Université Côte d'Azur, CNRS, INSERM, iBV, Parc Valrose, Nice, France.
authors.forename: Martine
authors.identifier: 0000-0001-9965-567X
authors.initials: M
authors.lastname: Bassilana
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002176:Candida albicans / Q000201:enzymology* / Q000254:growth & development* / Q000472:pathogenicity*; D002177:Candidiasis; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000378:metabolism*; D055786:Gene Knockout Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009024:Morphogenesis; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; C097313:ADP-ribosylation factor related proteins; D020727:ADP-Ribosylation Factors