title: Cell surface changes in the Candida albicans mitochondrial mutant goa1Δ are associated with reduced recognition by innate immune cells.
abstract: We have previously characterized several fungal-specific proteins from the human pathogen Candida albicans that either encode subunits of mitochondria Complex I (CI) of the electron transport chain (ETC) or regulate CI activity (Goa1p). Herein, the role of energy production and cell wall gene expression is investigated in the mitochondria mutant goa1Δ. We show that downregulation of cell wall-encoding genes in the goa1Δ results in sensitivity to cell wall inhibitors such as Congo red and Calcofluor white, reduced phagocytosis by a macrophage cell line, reduced recognition by macrophage receptors, and decreased expression of cytokines such as IL-6, IL-10 and IFN-γ. In spite of the reduced recognition by macrophages, the goa1Δ is still killed to the same extent as control strains. We also demonstrate that expression of the epithelial cell receptors E-cadherin and EGFR is also reduced in the presence of goa1Δ. Together, our data demonstrate the importance of mitochondria in the expression of cell wall biomolecules and the interaction of C. albicans with innate immune and epithelial cells. Our underlying premise is thatmitochondrial proteins such as Goa1p and other fungal-specific mitochondrial proteins regulate critical functions in cell growth and in virulence. As such, they remain as valid drug targets for antifungal drug discovery.
authors.affiliation: Department of Microbiology & Immunology, Georgetown University Medical Center, Washington DC 20057, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: She
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Calderone
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005816:Genetic Complementation Test; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D013499:Surface Properties
chemical_list: D016207:Cytokines; D005656:Fungal Proteins