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Cited by 359

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A Drug-Sensitive Genetic Network Masks Fungi from the Immune System

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Wheeler, Robert T, Fink, Gerald R·2006·PLoS Pathogens
DOI 10.1371/journal.ppat.0020035
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Abstract

Fungal pathogens can be recognized by the immune system via their beta-glucan, a potent proinflammatory molecule that is present at high levels but is predominantly buried beneath a mannoprotein coat and invisible to the host. To investigate the nature and significance of "masking" this molecule, we characterized the mechanism of masking and consequences of unmasking for immune recognition. We found that the underlying beta-glucan in the cell wall of Candida albicans is unmasked by subinhibitory doses of the antifungal drug caspofungin, causing the exposed fungi to elicit a stronger immune response. Using a library of bakers' yeast (Saccharomyces cerevisiae) mutants, we uncovered a conserved genetic network that is required for concealing beta-glucan from the immune system and limiting the host response. Perturbation of parts of this network in the pathogen C. albicans caused unmasking of its beta-glucan, leading to increased beta-glucan receptor-dependent elicitation of key proinflammatory cytokines from primary mouse macrophages. By creating an anti-inflammatory barrier to mask beta-glucan, opportunistic fungi may promote commensal colonization and have an increased propensity for causing disease. Targeting the widely conserved gene network required for creating and maintaining this barrier may lead to novel broad-spectrum antimycotics.

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Research works printed but not linked: 35

  1. 2002, Phagocytosis of microbes: Complexity in action., Annu Rev Immunol, 20, 825, 10.1146/annurev.immunol.20.103001.114744 · DOI · Paper page
  2. 2004, Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program., J Clin Microbiol, 42, 1519, 10.1128/JCM.42.4.1519-1527.2004 · DOI · Paper page
  3. 2005, Aspergillus infections in transplant recipients., Clin Microbiol Rev, 18, 44, 10.1128/CMR.18.1.44-69.2005 · DOI · Paper page
  4. 2004, Candida albicans cell wall glycans, host receptors and responses: Elements for a decisive crosstalk., Curr Opin Microbiol, 7, 342, 10.1016/j.mib.2004.06.011 · DOI
  5. 1998, Cell wall and secreted proteins of Candida albicans: Identification, function, and expression., Microbiol Mol Biol Rev, 62, 130, 10.1128/MMBR.62.1.130-180.1998 · DOI · Paper page
  6. 2005, A novel glyco-conjugate vaccine against fungal pathogens., J Exp Med, 202, 597, 10.1084/jem.20050749 · DOI · Paper page
  7. 2005, Immune recognition of fungal beta-glucans., Cell Microbiol, 7, 471, 10.1111/j.1462-5822.2005.00505.x · DOI · Paper page
  8. 2003, Echinocandin antifungal drugs., Lancet, 362, 1142, 10.1016/S0140-6736(03)14472-8 · DOI · Paper page
  9. OrleanP 1997 Biogenesis of yeast wall and surface components. In: PringleJRBroachJRJonesEW The molecular and cellular biology of the yeast Saccharomyces cerevisiae Plainview (New York) Cold Spring Harbor Laboratory Press 1131 p.
  10. 1991, The location of (1-]3)-beta-glucans in the walls of pollen tubes of Nicotiana alata using a (1-]3)-beta-glucan-specific monoclonal-antibody., Planta, 185, 1
  11. 2005, Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments., EMBO J, 24, 1277, 10.1038/sj.emboj.7600594 · DOI · Paper page
  12. 2005, Glucan-associated protein modulations and ultrastructural changes of the cell wall in Candida albicans treated with micafungin, a water-soluble, lipopeptide antimycotic., J Chemother, 17, 409, 10.1179/joc.2005.17.4.409 · doi:10.1179/joc.2005.17.4.409
  13. 2001, A protein interaction map for cell polarity development., J Cell Biol, 154, 549, 10.1083/jcb.200104057 · DOI · Paper page
  14. 2004, Mechanisms of polarized growth and organelle segregation in yeast., Annu Rev Cell Dev Biol, 20, 559, 10.1146/annurev.cellbio.20.010403.103108 · DOI · Paper page
  15. 2004, Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin., Genetics, 167, 35, 10.1534/genetics.167.1.35 · DOI · Paper page
  16. 1998, The pH of the host niche controls gene expression in and virulence of Candida albicans., Infect Immun, 66, 3317, 10.1128/IAI.66.7.3317-3325.1998 · DOI · Paper page
  17. 1997, Architecture of the yeast cell wall. Beta(1—>6)-glucan interconnects mannoprotein, beta(1—>)3-glucan, and chitin., J Biol Chem, 272, 17762, 10.1074/jbc.272.28.17762 · DOI · Paper page
  18. 2004, KRE5 gene null mutant strains of Candida albicans are avirulent and have altered cell wall composition and hypha formation properties., Eukaryot Cell, 3, 1423, 10.1128/EC.3.6.1423-1432.2004 · DOI
  19. 1984, Saccharomyces cerevisiae mannoproteins form an external cell wall layer that determines wall porosity., J Bacteriol, 159, 1018, 10.1128/JB.159.3.1018-1026.1984 · DOI · Paper page
  20. 1991, Passage of molecules through yeast cell walls: A brief essay-review., Yeast, 7, 313, 10.1002/yea.320070402 · DOI
  21. MathewsHLWitek-JanusekL 2002 Host defense against oral, esophageal, and gastrointestinal candidiasis. In: CalderoneRA Candida and candidiasis Washington (D. C.) ASM Press pp. 179 192
  22. 2004, Genetic analysis of innate immunity in resistance to Candida albicans., Genes Immun, 5, 576, 10.1038/sj.gene.6364130 · DOI
  23. 2005, Role of anti-beta-glucan antibody in host defense against fungi., FEMS Immunol Med Microbiol, 44, 99, 10.1016/j.femsim.2004.12.012 · DOI
  24. 2005, Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1., Infect Immun, 73, 1553, 10.1128/IAI.73.3.1553-1560.2005 · DOI
  25. 2003, Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor., J Exp Med, 198, 1677, 10.1084/jem.20030932 · DOI · Paper page
  26. 1999, Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis., Science, 285, 901, 10.1126/science.285.5429.901 · DOI · Paper page
  27. 1993, Isogenic strain construction and gene mapping in Candida albicans., Genetics, 134, 717, 10.1093/genetics/134.3.717 · DOI · Paper page
  28. 2003, Dectin-1 mediates the biological effects of beta-glucans., J Exp Med, 197, 1119, 10.1084/jem.20021890 · DOI · Paper page
  29. 2001, Crystal structure of a neutralizing human IGG against HIV-1: A template for vaccine design., Science, 293, 1155, 10.1126/science.1061692 · DOI · Paper page
  30. 2001, Crystal structure of the C-type lectin-like domain from the human hematopoietic cell receptor CD69., J Biol Chem, 276, 7312, 10.1074/jbc.M008573200 · doi:10.1074/jbc.m008573200
  31. 1997, PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression., Mol Cell Biol, 17, 5960, 10.1128/MCB.17.10.5960 · DOI · Paper page
  32. 2003, A Saccharomyces cerevisiae genome-wide mutant screen for altered sensitivity to K1 killer toxin., Genetics, 163, 875, 10.1093/genetics/163.3.875 · DOI
  33. el-Sherbeini M, Clemas JA, 1995, Cloning and characterization of GNS1: A Saccharomyces cerevisiae gene involved in synthesis of 1,3-beta-glucan in vitro., J Bacteriol, 177, 3227, 10.1128/JB.177.11.3227-3234.1995 · DOI
  34. 1998, Involvement of protein N-glycosyl chain glucosylation and processing in the biosynthesis of cell wall beta-1,6-glucan of Saccharomyces cerevisiae., Genetics, 149, 843, 10.1093/genetics/149.2.843 · DOI
  35. 2002, Mutations in Fks1p affect the cell wall content of beta-1,3- and beta-1,6-glucan in Saccharomyces cerevisiae., Yeast, 19, 671, 10.1002/yea.866 · DOI

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Metadata

Authors
Wheeler, R. T., & Fink, G. R.
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2006-04-28
Volume
2
Issue
4
Pages
e35
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.0020035
OpenAlex
W2074233079
Cited by
359
References
4
FWCI
17.40
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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Wheeler, R. T., & Fink, G. R. (2006). A Drug-Sensitive Genetic Network Masks Fungi from the Immune System. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.0020035

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