Distinct roles of the 7-transmembrane receptor protein Rta3 in regulating the asymmetric distribution of phosphatidylcholine across the plasma membrane and biofilm formation in Candida albicans.
Cell Microbiol
; 19(12)2017 12.
Article
em En
| MEDLINE
| ID: mdl-28745020
ABSTRACT
Fungal pathogens such as Candida albicans exhibit several survival mechanisms to evade attack by antifungals and colonise host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain topology, similar to the G-protein-coupled receptors and is unique to the fungal kingdom. Our findings point towards a role for the plasma membrane localised Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics. Concurrent with miltefosine susceptibility, the rta3Δ/Δ strain displays increased inward translocation (flip) of fluorophore-labelled phosphatidylcholine (PC) across the plasma membrane attributed to enhanced PC-specific flippase activity. We also assign a novel role to Rta3 in the Bcr1-regulated pathway for in vivo biofilm development. Transcriptome analysis reveals that Rta3 regulates expression of Bcr1 target genes involved in cell surface properties, adhesion, and hyphal growth. We show that rta3Δ/Δ mutant is biofilm-defective in a rat venous catheter model of infection and that BCR1 overexpression rescues this defect, indicating that Bcr1 functions downstream of Rta3 to mediate biofilm formation in C. albicans. The identification of this novel Rta3-dependent regulatory network that governs biofilm formation and PC asymmetry across the plasma membrane will provide important insights into C. albicans pathogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilcolinas
/
Candida albicans
/
Proteínas Fúngicas
/
Membrana Celular
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Biofilmes
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Microbiol
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Índia