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Reverse genetics in Candida albicans predicts ARF cycling is essential for drug resistance and virulence

By Elias Epp, Ghyslaine Vanier, Doreen Harcus, Anna Y Lee, Gregor Jansen, Michael Hallett, Don C Sheppard, David Y Thomas, Carol A Munro, Alaka Mullick and Malcolm Whiteway


Peer reviewedPublisher PD

Topics: QH426 Genetics, QH426
Year: 2010
DOI identifier: 10.1371/journal.ppat.1000753
OAI identifier:

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  8. (2000). Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2. doi
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  10. (1992). Brefeldin A binds to glutathione S-transferase and is secreted as glutathione and cysteine conjugates by Chinese hamster ovary cells.
  11. (1996). Brefeldin A is a potent inducer of apoptosis in human cancer cells independently of p53. doi
  12. (1998). Brefeldin A-mediated apoptosis requires the activation of caspases and is inhibited by Bcl-2. Exp Cell Res doi
  13. (2003). Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. doi
  14. (2002). Calcineurin is essential for survival during membrane stress in Candida albicans. doi
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  16. (2005). Calcineurin is required for Candida albicans to survive calcium stress in serum. doi
  17. (2002). Candida albicans Mds3p, a conserved regulator of pH responses and virulence identified through insertional mutagenesis.
  18. (2003). Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. doi
  19. (2002). Candida albicans sterol C-14 reductase, encoded by the ERG24 gene, as a potential antifungal target site. doi
  20. (2008). Candida infection in HIV positive patients 1985–2007. doi
  21. (2008). Changing epidemiology of systemic fungal infections. doi
  22. (2008). Chemical-genetic approaches for exploring the mode of action of natural products. doi
  23. (2009). Chemogenomic profiling predicts antifungal synergies. doi
  24. (2004). Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. doi
  25. (2009). Clinical practice guidelines for the management of candidiasis: doi
  26. (2006). Control of the C. albicans cell wall damage response by transcriptional regulator Cas5. PLoS Pathog 2: doi
  27. (2003). Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism. doi
  28. (2006). CRZ1, a target of the calcineurin pathway in Candida albicans. doi
  29. (1958). Decumbin, a new compound from a species of Penicillium. doi
  30. (2004). Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse strain. doi
  31. (2009). Effluxmediated antifungal drug resistance. Clin Microbiol Rev 22: 291–321, table of contents.
  32. (2000). Elucidation of strict structural requirements of brefeldin A as an inducer of differentiation and apoptosis. doi
  33. (2005). Emerging fungal diseases. doi
  34. (2007). Epidemiology of invasive candidiasis: a persistent public health problem. doi
  35. (2009). Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). doi
  36. (2008). Evolution of eukaryotic transcription circuits. doi
  37. (2000). Fluconazole plus cyclosporine: a fungicidal combination effective against experimental endocarditis due to Candida albicans. doi
  38. (1999). GEFs: structural basis for their activation of small GTP-binding proteins. doi
  39. (2007). Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. doi
  40. (2005). Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. doi
  41. (2007). Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. doi
  42. (2009). Genome-wide mapping of the coactivator Ada2p yields insight into the functional roles of SAGA/ADA complex in Candida albicans. doi
  43. (2008). Genomewide location analysis of Candida albicans Upc2p, a regulator of sterol metabolism and azole drug resistance. doi
  44. (2007). Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. doi
  45. (2009). Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. doi
  46. (2009). Hidden killers: persistence of opportunistic fungal pathogens in the human host. doi
  47. (2009). Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog 5: doi
  48. (2005). Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. doi
  49. (2008). In search of the holy grail of antifungal therapy.
  50. (1998). In-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans. doi
  51. (1999). Induction of terminal differentiation and apoptosis in human colonic carcinoma cells by brefeldin A, a drug affecting ganglioside biosynthesis. doi
  52. (2006). Invasive Fungal Pathogens: Current Epidemiological Trends. doi
  53. (2006). Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway. doi
  54. (2006). Microarrays for studying pathogenicity in Candida albicans; doi
  55. (1996). Molecular and phenotypic analysis of the S. cerevisiae MNN10 gene identifies a family of related glycosyltransferases. doi
  56. (1998). Molecules in the ARF orbit. doi
  57. (2007). Morphogenesis in Candida albicans. doi
  58. (1999). Mutants of Kluyveromyces lactis with altered protein glycosylation are affected in cell wall morphogenesis. doi
  59. (2009). Nantel A doi
  60. (2003). New modules for PCR-based gene targeting in Candida albicans: rapid and efficient gene targeting using 100 bp of flanking homology region.
  61. (1992). One-step transformation of yeast in stationary phase. doi
  62. (2004). Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. doi
  63. (2008). Paradoxical growth effects of the echinocandins caspofungin and micafungin, but not of anidulafungin, on clinical isolates of Candida albicans and C. dubliniensis. doi
  64. (2008). PCR-based gene targeting in Candida albicans. doi
  65. (2000). Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans. doi
  66. (2001). Preparation and evaluation of sulfide derivatives of the antibiotic brefeldin a as potential prodrug candidates with enhanced aqueous solubilities. doi
  67. (1991). Preparation of high molecular weight RNA. doi
  68. (2004). Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. doi
  69. (2007). Recent advances and challenges in the treatment of invasive fungal infections. doi
  70. (1908). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard. doi
  71. (1908). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard-Second Edition. doi
  72. (2008). Regulation of actin cytoskeleton dynamics by Arf-family GTPases. doi
  73. (1999). Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins with overlapping function. doi
  74. (2002). RHO-GTPases and cancer. doi
  75. (1996). Saccharomyces cerevisiae Gcs1 is an ADP-ribosylation factor GTPaseactivating protein. doi
  76. (2005). SAGA unveiled. doi
  77. (2007). Sequence resources at the Candida Genome Database. doi
  78. (2005). Strains and Strategies for Large-Scale Gene Deletion Studies of the Diploid Human Fungal Pathogen Candida albicans. Eukaryotic Cell. doi
  79. (2008). Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance. doi
  80. (1998). Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching.
  81. (1999). Structural basis for the inhibitory effect of brefeldin A on guanine nucleotide-exchange proteins for ADP-ribosylation factors. doi
  82. (2003). Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. doi
  83. (2001). Structures of yeast ARF2 and ARL1: distinct roles for the N terminus in the structure and function of ARF family GTPases. doi
  84. (1997). Synthesis and activity of brefeldin a analogs as inducers of cancer cell differentiation and apoptosis. doi
  85. (2006). Synthesis and anticancer activity of brefeldin A ester derivatives. doi
  86. (2003). Targeting RAS signalling pathways in cancer therapy. doi
  87. (2009). Targeting virulence: a new paradigm for antifungals. doi
  88. (2002). The direct cost and incidence of systemic fungal infections. doi
  89. (2008). The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype. doi
  90. (2001). The Gcs1 and Age2 ArfGAP proteins provide overlapping essential function for transport from the yeast trans-Golgi network. doi
  91. (2002). The genetic basis of fluconazole resistance development in Candida albicans. doi
  92. (1953). The problem of synergism and antagonism of combined drugs.
  93. (2009). The Saccharomyces Genome Database, (as of
  94. (2004). The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. doi
  95. (2007). The small G proteins of the Arf family and their regulators. doi
  96. (2007). The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. doi
  97. (2007). The zinc cluster transcription factor Tac1p regulates PDR16 expression in Candida albicans. doi
  98. (2006). Time course of microbiologic outcome and gene expression in Candida albicans during and following in vitro and in vivo exposure to fluconazole. doi
  99. (2008). Transcription factor substitution during the evolution of fungal ribosome regulation. doi
  100. (2009). Widespread occurrence of chromosomal aneuploidy following the routine production of Candida albicans mutants. FEMS Yeast Res. doi
  101. (1995). Yeast glycosylation mutants are sensitive to aminoglycosides. doi

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