Mannosylation in Candida albicans: role in cell wall function and immune recognition

The fungal cell wall is a dynamic organelle required for cell shape, protection against the environment and, in pathogenic species, recognition by the innate immune system. The outer layer of the cell wall is comprised of glycosylated mannoproteins with the majority of these post‐translational modifications being the addition of O‐ and N‐linked mannosides. These polysaccharides are exposed on the outer surface of the fungal cell wall and are, therefore, the first point of contact between the fungus and the host immune system. This review focuses on O‐ and N‐linked mannan biosynthesis in the fungal pathogen Candida albicans and highlights new insights gained from the characterization of mannosylation mutants into the role of these cell wall components in host–fungus interactions. In addition, we discuss the use of fungal mannan as a diagnostic marker of fungal disease.

[1]  Alistair J. P. Brown,et al.  Role of the Candida albicans MNN1 gene family in cell wall structure and virulence , 2013, BMC Research Notes.

[2]  Evolution and homoplasy at the Bem6 microsatellite locus in three sweetpotato whitefly (Bemisia tabaci) cryptic species , 2013, BMC Research Notes.

[3]  Jennifer R Linden,et al.  The role of galectin‐3 in phagocytosis of Candida albicans and Candida parapsilosis by human neutrophils , 2013, Cellular microbiology.

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

[5]  S. Kaesler,et al.  Glycosylation of Candida albicans Cell Wall Proteins Is Critical for Induction of Innate Immune Responses and Apoptosis of Epithelial Cells , 2012, PloS one.

[6]  B. Coddeville,et al.  Members 5 and 6 of the Candida albicans BMT family encode enzymes acting specifically on β-mannosylation of the phospholipomannan cell-wall glycosphingolipid. , 2012, Glycobiology.

[7]  Bernhard Hube,et al.  Importance of the Candida albicans cell wall during commensalism and infection. , 2012, Current opinion in microbiology.

[8]  Teresa R. O’Meara,et al.  The Cryptococcus neoformans Capsule: a Sword and a Shield , 2012, Clinical Microbiology Reviews.

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

[10]  T. Kozel,et al.  CrAg lateral flow assay for cryptococcosis. , 2012, Expert opinion on medical diagnostics.

[11]  J. Luna-Arias,et al.  Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis , 2012, Biochemical and biophysical research communications.

[12]  N. Gow,et al.  Stage Specific Assessment of Candida albicans Phagocytosis by Macrophages Identifies Cell Wall Composition and Morphogenesis as Key Determinants , 2012, PLoS pathogens.

[13]  J. Hirabayashi,et al.  Difference in Fine Specificity to Polysaccharides of Candida albicans Mannoprotein between Mouse SIGNR1 and Human DC-SIGN , 2012, Infection and Immunity.

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

[15]  K. Kuchler,et al.  Efg1 Controls Caspofungin-Induced Cell Aggregation of Candida albicans through the Adhesin Als1 , 2011, Eukaryotic Cell.

[16]  S. Smeekens,et al.  The classical CD14++CD16− monocytes, but not the patrolling CD14+CD16+ monocytes, promote Th17 responses to Candida albicans , 2011, European journal of immunology.

[17]  Z. Khan,et al.  Value of (1-3)-β-d-glucan, Candida mannan and Candida DNA detection in the diagnosis of candidaemia. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[18]  N. Gow,et al.  Candida albicans Cell Wall Glycosylation May Be Indirectly Required for Activation of Epithelial Cell Proinflammatory Responses , 2011, Infection and Immunity.

[19]  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.

[20]  V. Anttila,et al.  Factors influencing the performance level of Candida mannan antigen testing in allogeneic stem cell transplant recipients not receiving fluconazole prophylaxis , 2011, Transplant infectious disease : an official journal of the Transplantation Society.

[21]  J. Ernst,et al.  Signaling the glycoshield: maintenance of the Candida albicans cell wall. , 2011, International journal of medical microbiology : IJMM.

[22]  K. Takahara,et al.  C‐type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin‐1 , 2011, European journal of immunology.

[23]  J. Ernst,et al.  Damage to the glycoshield activates PMT‐directed O‐mannosylation via the Msb2–Cek1 pathway in Candida albicans , 2011, Molecular microbiology.

[24]  小野 聡,et al.  樹状細胞 (dendritic cell) , 2011 .

[25]  N. Gow,et al.  Glycosylation status of the C. albicans cell wall affects the efficiency of neutrophil phagocytosis and killing but not cytokine signaling , 2011, Medical mycology.

[26]  T. Calandra,et al.  The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia , 2010, Critical care.

[27]  G. Garlet,et al.  Absence of functional TLR4 impairs response of macrophages after Candida albicans infection. , 2010, Medical mycology.

[28]  L. Joosten,et al.  Variable recognition of Candida albicans strains by TLR4 and lectin recognition receptors. , 2010, Medical mycology.

[29]  S. Smeekens,et al.  The Candida Th17 response is dependent on mannan- and beta-glucan-induced prostaglandin E2. , 2010, International immunology.

[30]  Suhail Ahmad,et al.  Levels of (1→3)-β-D-glucan, Candida mannan and Candida DNA in serum samples of pediatric cancer patients colonized with Candida species , 2010, BMC infectious diseases.

[31]  J. Konopka,et al.  Recognition of Yeast by Murine Macrophages Requires Mannan but Not Glucan , 2010, Eukaryotic Cell.

[32]  C. Leslie,et al.  Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans , 2010, The Journal of Biological Chemistry.

[33]  L. Larsson,et al.  Detection of candidaemia in patients with and without underlying haematological disease. , 2010, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[34]  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.

[35]  M. Netea,et al.  A Multifunctional Mannosyltransferase Family in Candida albicans Determines Cell Wall Mannan Structure and Host-Fungus Interactions , 2010, The Journal of Biological Chemistry.

[36]  N. Gow,et al.  Contribution of Candida albicans Cell Wall Components to Recognition by and Escape from Murine Macrophages , 2010, Infection and Immunity.

[37]  Aseem Kumar,et al.  Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006) , 2010 .

[38]  N. Gow,et al.  Protein glycosylation in Candida. , 2009, Future microbiology.

[39]  Y. Okawa,et al.  The cell wall galactomannan antigen from Malassezia furfur and Malassezia pachydermatis contains beta-1,6-linked linear galactofuranosyl residues and its detection has diagnostic potential. , 2009, Microbiology.

[40]  Yong-nian Shen,et al.  Candida albicans phospholipomannan triggers inflammatory responses of human keratinocytes through Toll‐like receptor 2 , 2009, Experimental dermatology.

[41]  S. Akira,et al.  Toll-Like Receptor 9-Dependent Activation of Myeloid Dendritic Cells by Deoxynucleic Acids from Candida albicans , 2009, Infection and Immunity.

[42]  R. Bernsen,et al.  Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever. , 2009, Journal of medical microbiology.

[43]  François Gouin,et al.  Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: A multicenter, prospective, observational study in France (2005–2006) , 2009, Critical care medicine.

[44]  Osamu Takeuchi,et al.  C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia , 2009, Proceedings of the National Academy of Sciences.

[45]  S. Yamasaki,et al.  C-type lectin Mincle is an activating receptor for pathogenic fungus , 2009 .

[46]  Gerald R. Fink,et al.  Dynamic, Morphotype-Specific Candida albicans β-Glucan Exposure during Infection and Drug Treatment , 2008, PLoS pathogens.

[47]  Alessandra Cambi,et al.  Dendritic Cell Interaction with Candida albicans Critically Depends on N-Linked Mannan* , 2008, Journal of Biological Chemistry.

[48]  Christine A. Wells,et al.  The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component of the Innate Immune Response to Candida albicans1 , 2008, The Journal of Immunology.

[49]  Emmanuel Maes,et al.  Identification of a New Family of Genes Involved in β-1,2-Mannosylation of Glycans in Pichia pastoris and Candida albicans* , 2008, Journal of Biological Chemistry.

[50]  N. Gow,et al.  Stimulation of Chitin Synthesis Rescues Candida albicans from Echinocandins , 2008, PLoS pathogens.

[51]  M. Pfaller,et al.  Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection. , 2008, Diagnostic microbiology and infectious disease.

[52]  M. Netea,et al.  An integrated model of the recognition of Candida albicans by the innate immune system , 2008, Nature Reviews Microbiology.

[53]  M. Netea,et al.  Endoplasmic Reticulum α-Glycosidases of Candida albicans Are Required for N Glycosylation, Cell Wall Integrity, and Normal Host-Fungus Interaction , 2007, Eukaryotic Cell.

[54]  E. Cenci,et al.  Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins. , 2007, Medical mycology.

[55]  J. Latgé The cell wall: a carbohydrate armour for the fungal cell , 2007, Molecular microbiology.

[56]  D. Singleton,et al.  Influence of outer region mannosylphosphorylation on N-glycan formation by Candida albicans: normal acid-stable N-glycan formation requires acid-labile mannosylphosphate addition. , 2007, Glycobiology.

[57]  Z. Khan,et al.  Comparative evaluation of (1, 3)-β-D-glucan, mannan and anti-mannan antibodies, and Candida species-specific snPCR in patients with candidemia , 2007, BMC infectious diseases.

[58]  M. Chamaillard,et al.  Specific Recognition of Candida albicans by Macrophages Requires Galectin-3 to Discriminate Saccharomyces cerevisiae and Needs Association with TLR2 for Signaling1 , 2006, The Journal of Immunology.

[59]  C. d’Enfert,et al.  Protein O-Mannosyltransferase Isoforms Regulate Biofilm Formation in Candida albicans , 2006, Antimicrobial Agents and Chemotherapy.

[60]  D. Hsu,et al.  Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans1 , 2006, The Journal of Immunology.

[61]  A. Mitchell,et al.  Function of Candida albicans Adhesin Hwp1 in Biofilm Formation , 2006, Eukaryotic Cell.

[62]  D. Soll,et al.  Candida albicans Als3p is required for wild-type biofilm formation on silicone elastomer surfaces. , 2006, Microbiology.

[63]  S. Free,et al.  The structure and synthesis of the fungal cell wall , 2006, BioEssays : news and reviews in molecular, cellular and developmental biology.

[64]  K. Garey,et al.  Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[65]  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.

[66]  Siamon Gordon,et al.  The carbohydrate-recognition domain of Dectin-2 is a C-type lectin with specificity for high mannose. , 2006, Glycobiology.

[67]  M. Cuenca‐Estrella,et al.  Epidemiology, Risk Factors, and Prognosis of Candida parapsilosis Bloodstream Infections: Case-Control Population-Based Surveillance Study of Patients in Barcelona, Spain, from 2002 to 2003 , 2006, Journal of Clinical Microbiology.

[68]  D. Kelleher,et al.  An evolving view of the eukaryotic oligosaccharyltransferase. , 2006, Glycobiology.

[69]  R. Lee,et al.  MNN5 Encodes an Iron-Regulated α-1,2-Mannosyltransferase Important for Protein Glycosylation, Cell Wall Integrity, Morphogenesis, and Virulence in Candida albicans , 2006, Eukaryotic Cell.

[70]  Alistair J. P. Brown,et al.  Outer Chain N-Glycans Are Required for Cell Wall Integrity and Virulence of Candida albicans* , 2006, Journal of Biological Chemistry.

[71]  J. Wendland,et al.  Candida albicans CHT3 encodes the functional homolog of the Cts1 chitinase of Saccharomyces cerevisiae. , 2005, Fungal genetics and biology : FG & B.

[72]  M. Schaller,et al.  Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases , 2005, Infection and Immunity.

[73]  J. Latgé,et al.  Galactomannoproteins of Aspergillus fumigatus , 2005, Eukaryotic Cell.

[74]  N. Gow,et al.  Candida albicans Pmr1p, a Secretory Pathway P-type Ca2+/Mn2+-ATPase, Is Required for Glycosylation and Virulence* , 2005, Journal of Biological Chemistry.

[75]  D. Singleton,et al.  Surface Hydrophobicity Changes of Two Candida albicans Serotype B mnn4Δ Mutants , 2005, Eukaryotic Cell.

[76]  S. Fridkin,et al.  Epidemiology and Predictors of Mortality in Cases of Candida Bloodstream Infection: Results from Population-Based Surveillance, Barcelona, Spain, from 2002 to 2003 , 2005, Journal of Clinical Microbiology.

[77]  A. Ellepola,et al.  Laboratory diagnosis of invasive candidiasis. , 2005, Journal of microbiology.

[78]  M. Ferguson,et al.  Mnt1p and Mnt2p of Candida albicans Are Partially Redundant α-1,2-Mannosyltransferases That Participate in O-Linked Mannosylation and Are Required for Adhesion and Virulence* , 2005, Journal of Biological Chemistry.

[79]  J. Ernst,et al.  PMT family of Candida albicans: five protein mannosyltransferase isoforms affect growth, morphogenesis and antifungal resistance , 2004, Molecular microbiology.

[80]  G. Strecker,et al.  Inactivation of CaMIT1 Inhibits Candida albicans Phospholipomannan β-Mannosylation, Reduces Virulence, and Alters Cell Wall Protein β-Mannosylation* , 2004, Journal of Biological Chemistry.

[81]  N. Gow,et al.  Loss of Cell Wall Mannosylphosphate in Candida albicans Does Not Influence Macrophage Recognition* , 2004, Journal of Biological Chemistry.

[82]  Siamon Gordon,et al.  The Role of SIGNR1 and the β-Glucan Receptor (Dectin-1) in the Nonopsonic Recognition of Yeast by Specific Macrophages1 , 2004, The Journal of Immunology.

[83]  G. Strecker,et al.  Inactivation of CaMIT1 inhibits Candida albicans phospholipomannan beta-mannosylation, reduces virulence, and alters cell wall protein beta-mannosylation. , 2004, The Journal of biological chemistry.

[84]  J. Peter-Katalinic,et al.  Beta-galactofuranose-containing O-linked oligosaccharides present in the cell wall peptidogalactomannan of Aspergillus fumigatus contain immunodominant epitopes. , 2003, Glycobiology.

[85]  M. Vidal,et al.  Mannose receptor contribution to Candida albicans phagocytosis by murine E‐clone J774 macrophages , 2003, Journal of leukocyte biology.

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

[87]  Alessandra Cambi,et al.  The C‐type lectin DC‐SIGN (CD209) is an antigen‐uptake receptor for Candida albicans on dendritic cells , 2003, European journal of immunology.

[88]  E. Nemoto,et al.  Saccharomyces cerevisiae‐ and Candida albicans‐Derived Mannan Induced Production of Tumor Necrosis Factor Alpha by Human Monocytes in a CD14‐ and Toll‐Like Receptor 4‐Dependent Manner , 2002, Microbiology and immunology.

[89]  L. Hoyer,et al.  The ALS gene family of Candida albicans. , 2001, Trends in microbiology.

[90]  J. Latgé,et al.  Molecular organization of the alkali-insoluble fraction of Aspergillus fumigatus cell wall. , 2000, The Journal of biological chemistry.

[91]  D. Poulain,et al.  β-1,2-Linked Oligomannosides from Candida albicans Bind to a 32-Kilodalton Macrophage Membrane Protein Homologous to the Mammalian Lectin Galectin-3 , 2000, Infection and Immunity.

[92]  R. Ritter,et al.  Identification of a Novel, Dendritic Cell-associated Molecule, Dectin-1, by Subtractive cDNA Cloning* , 2000, The Journal of Biological Chemistry.

[93]  J. Ernst,et al.  Morphogenesis, Adhesive Properties, and Antifungal Resistance Depend on the Pmt6 Protein Mannosyltransferase in the Fungal Pathogen Candida albicans , 2000, Journal of bacteriology.

[94]  S. Southard,et al.  Molecular Analysis of the Candida albicans Homolog of Saccharomyces cerevisiae MNN9, Required for Glycosylation of Cell Wall Mannoproteins , 1999, Journal of bacteriology.

[95]  H. Bussey,et al.  Mnt2p and Mnt3p of Saccharomyces cerevisiae are members of the Mnn1p family of alpha-1,3-mannosyltransferases responsible for adding the terminal mannose residues of O-linked oligosaccharides. , 1999, Glycobiology.

[96]  Daniel Poulain,et al.  New Enzyme Immunoassays for Sensitive Detection of CirculatingCandida albicans Mannan and Antimannan Antibodies: Useful Combined Test for Diagnosis of Systemic Candidiasis , 1999, Journal of Clinical Microbiology.

[97]  G. Strecker,et al.  Nature of Candida albicans-derived carbohydrate antigen recognized by a monoclonal antibody in patient sera and distribution over Candida species. , 1998, FEMS microbiology letters.

[98]  A. Gurney,et al.  Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling , 1998, Nature.

[99]  Yan Feng,et al.  The involvement of mnn4 and mnn6 mutations in mannosylphosphorylation of O-linked oligosaccharide in yeast Saccharomyces cerevisiae. , 1998, Biochimica et biophysica acta.

[100]  S. Gordon,et al.  A Functional Soluble Form of the Murine Mannose Receptor Is Produced by Macrophages in Vitro and Is Present in Mouse Serum* , 1998, The Journal of Biological Chemistry.

[101]  P. Trinel,et al.  Early signal transduction induced by Candida albicans in macrophages through shedding of a glycolipid. , 1998, The Journal of infectious diseases.

[102]  K. Ziegelbauer,et al.  Multiple Functions of Pmt1p-mediated ProteinO-Mannosylation in the Fungal Pathogen Candida albicans * , 1998, The Journal of Biological Chemistry.

[103]  A. Brown,et al.  Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[104]  S. Munro,et al.  Multi‐protein complexes in the cis Golgi of Saccharomyces cerevisiae with α‐1,6‐mannosyltransferase activity , 1998, The EMBO journal.

[105]  K. Yoda,et al.  Novel membrane protein complexes for protein glycosylation in the yeast Golgi apparatus. , 1997, Biochemical and biophysical research communications.

[106]  T. Odani,et al.  Mannosylphosphate transfer to cell wall mannan is regulated by the transcriptional level of the MNN4 gene in Saccharomyces cerevisiae , 1997, FEBS letters.

[107]  A. Mitchell,et al.  Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors , 1997, Antimicrobial agents and chemotherapy.

[108]  C. Janeway,et al.  A human homologue of the Drosophila Toll protein signals activation of adaptive immunity , 1997, Nature.

[109]  T. Odani,et al.  Cloning and analysis of the MNN4 gene required for phosphorylation of N-linked oligosaccharides in Saccharomyces cerevisiae. , 1996, Glycobiology.

[110]  J. Latgé,et al.  Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis. , 1996, The Pediatric infectious disease journal.

[111]  V. Vetvicka,et al.  Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). , 1996, Journal of immunology.

[112]  J. Latgé,et al.  Chemical and immunological characterization of the extracellular galactomannan of Aspergillus fumigatus , 1994, Infection and immunity.

[113]  P. Trinel,et al.  The Candida albicans phospholipomannan induces in vitro production of tumour necrosis factor-alpha from human and murine macrophages. , 1994, Immunology.

[114]  Terri L. Gilbert,et al.  Cloning and analysis of the Saccharomyces cerevisiae MNN9 and MNN1 genes required for complex glycosylation of secreted proteins. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[115]  P. Capek,et al.  Ligand recognition by purified human mannose receptor. , 1992, Archives of biochemistry and biophysics.

[116]  L. Kaufman,et al.  Collaborative evaluation of antigen detection by a commercial latex agglutination test and enzyme immunoassay in the diagnosis of invasive candidiasis , 1990, Journal of clinical microbiology.

[117]  Y. Fukazawa Antigenic structure of Candida albicans. Immunochemical basis of the serologic specificity of the mannans in yeasts. , 1989, Immunology series.

[118]  Dr. Werner Mendling Vulvovaginal Candidosis , 1988, Springer Berlin Heidelberg.

[119]  J. Bennett,et al.  Diagnosis of systemic candidiasis by latex agglutination for serum antigen , 1985, Journal of clinical microbiology.

[120]  F. Odds,et al.  Distribution of pathogenic yeasts and humoral antibodies to candida among hospital inpatients. , 1980, Journal of clinical pathology.

[121]  C. Ballou,et al.  Biosynthesis of yeast mannan. Properties of a mannosylphosphate transferase in Saccharomyces cerevisiae. , 1978, The Journal of biological chemistry.