Cell Wall N-Linked Mannoprotein Biosynthesis Requires Goa1p, a Putative Regulator of Mitochondrial Complex I in Candida albicans

The Goa1p of Candida albicans regulates mitochondrial Complex I (CI) activities in its role as a putative CI accessory protein. Transcriptional profiling of goa1∆ revealed a down regulation of genes encoding β-oligomannosyl transferases. Herein, we present data on cell wall phenotypes of goa1∆ (strain GOA31). We used transmission electron microscopy (TEM), GPC/MALLS, and NMR to compare GOA31 to a gene-reconstituted strain (GOA32) and parental cells. We note by TEM a reduction in outer wall fibrils, increased inner wall transparency, and the loss of a defined wall layer close to the plasma membrane. GPC-MALLS revealed a reduction in high and intermediate Mw mannan by 85% in GOA31. A reduction of β-mannosyl but not α-mannosyl linkages was noted in GOA31 cells. β-(1,6)-linked glucan side chains were branched about twice as often but were shorter in length for GOA31. We conclude that mitochondrial CI energy production is highly integrated with cell wall formation. Our data also suggest that not all cell wall biosynthetic processes are dependent upon Goa1p even though it provides high levels of ATP to cells. The availability of both broadly conserved and fungal-specific mutants lacking CI subunit proteins should be useful in assessing functions of fungal-specific functions subunit proteins.

[1]  Yin Gao,et al.  Fungal‐specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis , 2015, Cellular microbiology.

[2]  J. Puthumana,et al.  Immune gene expression profile of Penaeus monodon in response to marine yeast glucan application and white spot syndrome virus challenge. , 2015, Fish & shellfish immunology.

[3]  S. Moreno,et al.  Interacting proteins of protein kinase A regulatory subunit in Saccharomyces cerevisiae. , 2014, Journal of proteomics.

[4]  E. Sánchez-León,et al.  The Spitzenkörper: a choreographer of fungal growth and morphogenesis. , 2014, Current opinion in microbiology.

[5]  Patricia M. Sikorski,et al.  The Rbf1, Hfl1 and Dbp4 of Candida albicans regulate common as well as transcription factor-specific mitochondrial and other cell activities , 2014, BMC Genomics.

[6]  B. Coddeville,et al.  Characterization of the recombinant Candida albicans β-1,2-mannosyltransferase that initiates the β-mannosylation of cell wall phosphopeptidomannan. , 2014, The Biochemical journal.

[7]  D. Poulain,et al.  Deficient Beta-Mannosylation of Candida albicans Phospholipomannan Affects the Proinflammatory Response in Macrophages , 2013, PloS one.

[8]  M. Netea,et al.  Novel Structural Features in Candida albicans Hyphal Glucan Provide a Basis for Differential Innate Immune Recognition of Hyphae Versus Yeast* , 2013, The Journal of Biological Chemistry.

[9]  M. Lorenz,et al.  Fungal Immune Evasion in a Model Host–Pathogen Interaction: Candida albicans Versus Macrophages , 2013, PLoS pathogens.

[10]  R. Calderone,et al.  Cell surface changes in the Candida albicans mitochondrial mutant goa1Δ are associated with reduced recognition by innate immune cells , 2013, Cellular microbiology.

[11]  N. Gow,et al.  Differential Virulence of Candida glabrata Glycosylation Mutants , 2013, The Journal of Biological Chemistry.

[12]  Margaret A. Johnson,et al.  Designing a new antifungal glycoconjugate vaccine. , 2013, Chemical Society reviews.

[13]  N. Gow,et al.  The Mnn2 Mannosyltransferase Family Modulates Mannoprotein Fibril Length, Immune Recognition and Virulence of Candida albicans , 2013, PLoS pathogens.

[14]  Christian M. Metallo,et al.  Understanding metabolic regulation and its influence on cell physiology. , 2013, Molecular cell.

[15]  Kun-Liang Guan,et al.  Nutrient sensing, metabolism, and cell growth control. , 2013, Molecular cell.

[16]  N. Gow,et al.  The Evolutionary Rewiring of Ubiquitination Targets Has Reprogrammed the Regulation of Carbon Assimilation in the Pathogenic Yeast Candida albicans , 2012, mBio.

[17]  R. Calderone,et al.  Caloric restriction restores the chronological life span of the Goa1 null mutant of Candida albicans in spite of high cell levels of ROS. , 2012, Fungal genetics and biology : FG & B.

[18]  N. Gow,et al.  Importance of the Candida albicans cell wall during commensalism and infection. , 2012, Current opinion in microbiology.

[19]  N. Gow,et al.  Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen , 2012, Cellular microbiology.

[20]  D. Bundle,et al.  Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis , 2012, PloS one.

[21]  K. Knagge,et al.  Mannan structural complexity is decreased when Candida albicans is cultivated in blood or serum at physiological temperature. , 2011, Carbohydrate research.

[22]  David L. Williams,et al.  C. albicans increases cell wall mannoprotein, but not mannan, in response to blood, serum and cultivation at physiological temperature. , 2011, Glycobiology.

[23]  S. Gamblin,et al.  AMP-activated protein kinase: nature's energy sensor. , 2011, Nature chemical biology.

[24]  Patricia M. Sikorski,et al.  Enzymatic Dysfunction of Mitochondrial Complex I of the Candida albicans goa1 Mutant Is Associated with Increased Reactive Oxidants and Cell Death , 2011, Eukaryotic Cell.

[25]  S. Akira,et al.  Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. , 2010, Immunity.

[26]  David L. Williams,et al.  The Candida albicans histidine kinase Chk1p: signaling and cell wall mannan. , 2009, Fungal genetics and biology : FG & B.

[27]  A. Vercesi,et al.  Goa1p of Candida albicans Localizes to the Mitochondria during Stress and Is Required for Mitochondrial Function and Virulence , 2009, Eukaryotic Cell.

[28]  D. Bundle,et al.  Synthetic glycopeptide vaccines combining β-mannan and peptide epitopes induce protection against candidiasis , 2008, Proceedings of the National Academy of Sciences.

[29]  Claire Collins,et al.  Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. , 2006, The Journal of clinical investigation.

[30]  J. Masuoka Surface Glycans of Candida albicans and Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges , 2004, Clinical Microbiology Reviews.

[31]  David L. Williams,et al.  Structural characterization of (1-->3)-beta-D-glucans isolated from blastospore and hyphal forms of Candida albicans. , 2003, Carbohydrate research.

[32]  Osamu Takeuchi,et al.  Candida albicans phospholipomannan is sensed through toll-like receptors. , 2003, The Journal of infectious diseases.

[33]  Veena P Menon,et al.  The role of the Candida albicans histidine kinase [CHK1) gene in the regulation of cell wall mannan and glucan biosynthesis. , 2003, FEMS yeast research.

[34]  P. Trinel,et al.  Peptides that mimic Candida albicans–derived β-1,2-linked mannosides , 2001 .

[35]  Gerald R. Fink,et al.  The glyoxylate cycle is required for fungal virulence , 2001, Nature.

[36]  M. Riesselman,et al.  Protection against Candidiasis by an Immunoglobulin G3 (IgG3) Monoclonal Antibody Specific for the Same Mannotriose as an IgM Protective Antibody , 2000, Infection and Immunity.

[37]  F. Kiss,et al.  Mitochondrial Function in Cell Wall Glycoprotein Synthesis in Saccharomyces cerevisiae NCYC 625 (Wild Type) and [rho0] Mutants , 1999, Applied and Environmental Microbiology.

[38]  J. Latgé,et al.  A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis , 1995, Journal of clinical microbiology.

[39]  P. Robbins,et al.  Architecture of the Yeast Cell Wall , 1995, The Journal of Biological Chemistry.

[40]  A. Brown,et al.  A hyphal-specific chitin synthase gene (CHS2) is not essential for growth, dimorphism, or virulence of Candida albicans. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[41]  R. Hector,et al.  Compounds active against cell walls of medically important fungi , 1993, Clinical Microbiology Reviews.

[42]  P. Gopal,et al.  Analysis of wall glucans from yeast, hyphal and germ-tube forming cells of Candida albicans. , 1984, Journal of general microbiology.

[43]  C. Ballou,et al.  Method for Fingerprinting Yeast Cell Wall Mannans , 1969, Journal of Bacteriology.

[44]  C. D. de Koster,et al.  Mass spectrometry-based proteomics of fungal wall glycoproteins. , 2008, Trends in microbiology.

[45]  K. Hellingwerf,et al.  Molecular organization of the cell wall of Candida albicans. , 2001, Medical mycology.

[46]  W. E. Scott,et al.  Polysaccharide conformation. Part VI. Computer model-building for linear and branched pyranoglycans. Correlations with biological function. Preliminary assessment of inter-residue forces in aqueous solution. Further interpretation of optical rotation in terms of chain conformation , 1971 .

[47]  F. Smith,et al.  COLORIMETRIC METHOD FOR DETER-MINATION OF SUGAR AND RELATED SUBSTANCE , 1956 .