Candida glabrata: a review of its features and resistance

Abstract

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    Lass-Flörl C (2009) The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 52:197–205

    PubMed  Google Scholar 

  2. 2.

    Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J (2012) Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance. FEMS Microbiol Rev 36(2):288–305. doi:10.1111/j.1574-6976.2011.00278.x

    PubMed  CAS  Google Scholar 

  3. 3.

    Odds FC (1988) Candida and candidosis, 2nd edn. Bailliere Tindall, London, UK

    Google Scholar 

  4. 4.

    Calderone RA (2002) Introduction and historical perspectives. In: Calderone RA (ed) Candida and candidiasis. ASM Press, Washington D.C., pp 15–25

    Google Scholar 

  5. 5.

    Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163

    PubMed Central  PubMed  CAS  Google Scholar 

  6. 6.

    Bassetti M, Righi E, Costa A et al (2006) Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis 6:21

    PubMed Central  PubMed  Google Scholar 

  7. 7.

    Colombo AL, Guimarães T, Silva LR et al (2007) Prospective observational study of candidemia in São Paulo, Brazil: incidence rate, epidemiology, and predictors of mortality. Infect Control Hosp Epidemiol 28:570–576

    PubMed  Google Scholar 

  8. 8.

    Chakrabarti A, Chatterjee SS, Rao KLN et al (2009) Recent experience with fungaemia: change in species distribution and azole resistance. Scand J Infect Dis 41:275–284

    PubMed  CAS  Google Scholar 

  9. 9.

    Hasan F, Xess I, Wang X, Jain N, Fries BC (2009) Biofilm formation in clinical Candida isolates and its association with virulence. Microbes Infect 11:753–761

    PubMed Central  PubMed  CAS  Google Scholar 

  10. 10.

    Krcmery V (1999) Torulopsis glabrata: an emerging yeast pathogen in cancer patients. Int J Antimicrob Agents 11:1–6

    PubMed  CAS  Google Scholar 

  11. 11.

    Krcmery V, Barnes AJ (2002) Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J Hosp Infect 50:243–260

    PubMed  CAS  Google Scholar 

  12. 12.

    Kaur R, Domergue R, Zupancic ML, Cormack BP (2005) A yeast by any other name: Candida glabrata and its interaction with the host. Curr Opin Microbiol 8:378–384

    PubMed  CAS  Google Scholar 

  13. 13.

    Pfaller MA, Diekema DJ (2004) Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida. Clin Microbiol Infect 10(Suppl 1):11–23

    PubMed  CAS  Google Scholar 

  14. 14.

    Bethea EK, Carver BJ, Montedonico AE, Reynolds TB (2010) The inositol regulon controls viability in Candida glabrata. Microbiology 156:452–462

    PubMed Central  PubMed  CAS  Google Scholar 

  15. 15.

    Sardi JCO, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJS (2013) Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. J Med Microbiol 62:10–24

    PubMed  CAS  Google Scholar 

  16. 16.

    Kim J, Sudbery P (2011) Candida albicans, a major human fungal pathogen. J Microbiol 49:171–177

    PubMed  Google Scholar 

  17. 17.

    Lim CS, Rosli R, Seow HF, Chong PP (2012) Candida and invasive candidiasis: back to basics. Eur J Clin Microbiol Infect Dis 31:21–31

    PubMed  Google Scholar 

  18. 18.

    Vincent JL, Rello J, Marshall J et al (2009) International study of the prevalence and outcomes of infection in intensive care units. JAMA 302:2323–2329

    PubMed  CAS  Google Scholar 

  19. 19.

    Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB (2006) Inflammatory response and clinical course of adult patients with nosocomial bloodstream infections caused by Candida spp. Clin Microbiol Infect 12:170–177

    PubMed  CAS  Google Scholar 

  20. 20.

    Vazquez JA, Dembry LM, Sanchez V et al (1998) Nosocomial Candida glabrata colonization: an epidemiologic study. J Clin Microbiol 36:421–426

    PubMed Central  PubMed  CAS  Google Scholar 

  21. 21.

    Vazquez JA, Sanchez V, Dmuchowski C, Dembry LM, Sobel JD, Zervos MJ (1993) Nosocomial acquisition of Candida albicans: an epidemiologic study. J Infect Dis 168:195–201

    PubMed  CAS  Google Scholar 

  22. 22.

    Reagan DR, Pfaller MA, Hollis RJ, Wenzel RP (1990) Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe. J Clin Microbiol 28:2733–2738

    PubMed Central  PubMed  CAS  Google Scholar 

  23. 23.

    Hagerty JA, Ortiz J, Reich D, Manzarbeitia C (2003) Fungal infections in solid organ transplant patients. Surg Infect (Larchmt) 4:263–271

    Google Scholar 

  24. 24.

    Kojic EM, Darouiche RO (2004) Candida infections of medical devices. Clin Microbiol Rev 17:255–267

    PubMed Central  PubMed  Google Scholar 

  25. 25.

    Samaranayake LP, Fidel PL, Naglik JR et al (2002) Fungal infections associated with HIV infection. Oral Dis 8:151–160

    PubMed  Google Scholar 

  26. 26.

    Rajendran R, Robertson DP, Hodge PJ, Lappin DF, Ramage G (2010) Hydrolytic enzyme production is associated with Candida albicans biofilm formation from patients with type 1 diabetes. Mycopathologia 170:229–235

    PubMed  CAS  Google Scholar 

  27. 27.

    Kuhn DM, Ghannoum MA (2004) Candida biofilms: antifungal resistance and emerging therapeutic options. Curr Opin Investig Drugs 5:186–197

    PubMed  CAS  Google Scholar 

  28. 28.

    de Almeida AA, Mesquita CS, Svidzinski TI, de Oliveira KM (2013) Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil. Rev Soc Bras Med Trop 46(3):335–339. doi:10.1590/0037-8682-0074-2012

    PubMed  Google Scholar 

  29. 29.

    Fidel PL Jr, Vazquez JA, Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev 12:80–96

    PubMed Central  PubMed  Google Scholar 

  30. 30.

    Dujon B, Sherman D, Fischer G et al (2004) Genome evolution in yeasts. Nature 430:35–44

    PubMed  Google Scholar 

  31. 31.

    Wolfe KH, Shields DC (1997) Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387:708–713

    PubMed  CAS  Google Scholar 

  32. 32.

    Butler G, Rasmussen MD, Lin MF et al (2009) Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657–662

    PubMed Central  PubMed  CAS  Google Scholar 

  33. 33.

    Brunke S, Hube B (2013) Two unlike cousins: Candida albicans and C. glabrata infection strategies. Cell Microbiol 15(5):701–708

    PubMed Central  PubMed  CAS  Google Scholar 

  34. 34.

    Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J (2011) Adherence and biofilm formation of non-Candida albicans Candida species. Trends Microbiol 19(5):241–247. doi:10.1016/j.tim.2011.02.003

    PubMed  CAS  Google Scholar 

  35. 35.

    Butler G, Kenny C, Fagan A, Kurischko C, Gaillardin C, Wolfe KH (2004) Evolution of the MAT locus and its Ho endonuclease in yeast species. Proc Natl Acad Sci U S A 101:1632–1637

    PubMed Central  PubMed  CAS  Google Scholar 

  36. 36.

    Hittinger CT, Rokas A, Carroll SB (2004) Parallel inactivation of multiple GAL pathway genes and ecological diversification in yeasts. Proc Natl Acad Sci U S A 101:14144–14149

    PubMed Central  PubMed  CAS  Google Scholar 

  37. 37.

    Roetzer A, Gabaldón T, Schüller C (2011) From Saccharomyces cerevisiae to Candida glabrata in a few easy steps: important adaptations for an opportunistic pathogen. FEMS Microbiol Lett 314:1–9

    PubMed Central  PubMed  CAS  Google Scholar 

  38. 38.

    Kramer A, Schwebke I, Kampf G (2006) How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis 6:130

    PubMed Central  PubMed  Google Scholar 

  39. 39.

    Cox GM, Harrison TS, Mcdade HC et al (2003) Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun 71(1):173–180

    PubMed Central  PubMed  CAS  Google Scholar 

  40. 40.

    Nicola AM, Casadevall A, Goldman DL (2008) Fungal killing by mammalian phagocytic cells. Curr Opin Microbiol 11(4):313–317

    PubMed Central  PubMed  CAS  Google Scholar 

  41. 41.

    Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223

    PubMed Central  PubMed  CAS  Google Scholar 

  42. 42.

    Nakagawa Y, Kanbe T, Mizuguchi I (2003) Disruption of the human pathogenic yeast Candida albicans catalase gene decreases survival in mouse-model infection and elevates susceptibility to higher temperature and to detergents. Microbiol Immunol 47(6):395–403

    PubMed  CAS  Google Scholar 

  43. 43.

    Roetzer A, Gratz N, Kovarik P, Schüller C (2010) Autophagy supports Candida glabrata survival during phagocytosis. Cell Microbiol 12(2):199–216

    PubMed Central  PubMed  CAS  Google Scholar 

  44. 44.

    Saijo T, Miyazaki T, Izumikawa K et al (2010) Skn7p is involved in oxidative stress response and virulence of Candida glabrata. Mycopathologia 169(2):81–90

    PubMed  CAS  Google Scholar 

  45. 45.

    Lee J, Godon C, Lagniel G et al (1999) Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem 274(23):16040–16046

    PubMed  CAS  Google Scholar 

  46. 46.

    Gulshan K, Lee SS, Moye-Rowley WS (2011) Differential oxidant tolerance determined by the key transcription factor Yap1 is controlled by levels of the Yap1-binding protein, Ybp1. J Biol Chem 286(39):34071–34081

    PubMed Central  PubMed  CAS  Google Scholar 

  47. 47.

    Roetzer A, Klopf E, Gratz N et al (2011) Regulation of Candida glabrata oxidative stress resistance is adapted to host environment. FEBS Lett 585(2):319–327

    PubMed Central  PubMed  CAS  Google Scholar 

  48. 48.

    Kaur R, Ma B, Cormack BP (2007) A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata. Proc Natl Acad Sci U S A 104(18):7628–7633

    PubMed Central  PubMed  CAS  Google Scholar 

  49. 49.

    Lorenz MC, Bender JA, Fink GR (2004) Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot Cell 3(5):1076–1087

    PubMed Central  PubMed  CAS  Google Scholar 

  50. 50.

    Roetzer A, Gregori C, Jennings AM et al (2008) Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors. Mol Microbiol 69(3):603–620

    PubMed Central  PubMed  CAS  Google Scholar 

  51. 51.

    Seider K, Brunke S, Schild L et al (2011) The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J Immunol 187(6):3072–3086

    PubMed  CAS  Google Scholar 

  52. 52.

    Klionsky DJ (2004) Cell biology: regulated self-cannibalism. Nature 431(7004):31–32

    PubMed  CAS  Google Scholar 

  53. 53.

    Klionsky DJ (2005) Autophagy. Curr Biol 15(8):R282–R283

    PubMed  CAS  Google Scholar 

  54. 54.

    Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9(10):1102–1109

    PubMed  CAS  Google Scholar 

  55. 55.

    Verstrepen KJ, Jansen A, Lewitter F, Fink GR (2005) Intragenic tandem repeats generate functional variability. Nat Genet 37(9):986–990

    PubMed Central  PubMed  CAS  Google Scholar 

  56. 56.

    Sundstrom P (2002) Adhesion in Candida spp. Cell Microbiol 4(8):461–469

    PubMed  CAS  Google Scholar 

  57. 57.

    Ruan SY, Hsueh PR (2009) Invasive candidiasis: an overview from Taiwan. J Formos Med Assoc 108(6):443–451

    PubMed  CAS  Google Scholar 

  58. 58.

    Kraneveld EA, De Soet JJ, Deng DM et al (2011) Identification and differential gene expression of adhesin-like wall proteins in Candida glabrata biofilms. Mycopathologia 172:415–427. doi:10.1007/ s11046-011-9446-2

    PubMed  CAS  Google Scholar 

  59. 59.

    De Groot PW, Kraneveld EA, Yin QY et al (2008) The cell wall of the human pathogen Candida glabrata: differential incorporation of novel adhesin-like wall proteins. Eukaryot Cell 7(11):1951–1964

    PubMed Central  PubMed  Google Scholar 

  60. 60.

    Domergue R, Castaño I, De Las Peñas A et al (2005) Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science 308(5723):866–870

    PubMed  CAS  Google Scholar 

  61. 61.

    Castaño I, Pan SJ, Zupancic M, Hennequin C, Dujon B, Cormack BP (2005) Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata. Mol Microbiol 55(4):1246–1258

    PubMed  Google Scholar 

  62. 62.

    Jandric Z, Schüller C (2011) Stress response in Candida glabrata: pieces of a fragmented picture. Future Microbiol 6(12):1475–1484

    PubMed  Google Scholar 

  63. 63.

    Silva S, Henriques M, Hayes A, Oliveira R, Azeredo J, Williams DW (2011) Candida glabrata and Candida albicans co-infection of an in vitro oral epithelium. J Oral Pathol Med 40(5):421–427. doi:10.1111/j.1600-0714.2010.00981

    PubMed  Google Scholar 

  64. 64.

    Jayatilake JA, Samaranayake YH, Cheung LK, Samaranayake LP (2006) Quantitative evaluation of tissue invasion by wild type, hyphal and SAP mutants of Candida albicans, and non-albicans Candida species in reconstituted human oral epithelium. J Oral Pathol Med 35(8):484–491

    PubMed  CAS  Google Scholar 

  65. 65.

    Tamura NK, Negri MF, Bonassoli LA, Svidzinski TI (2007) Virulence factors for Candida spp recovered from intravascular catheters and hospital workers hands. Rev Soc Bras Med Trop 40:91–93

    PubMed  Google Scholar 

  66. 66.

    Silva S, Henriques M, Martins A, Oliveira R, Williams D, Azeredo J (2009) Biofilms of non-Candida albicans Candida species: quantification, structure and matrix composition. Med Mycol 47:681–689

    PubMed  CAS  Google Scholar 

  67. 67.

    Iraqui I, Garcia-Sanchez S, Aubert S et al (2005) The Yak1p kinase controls expression of adhesins and biofilm formation in Candida glabrata in a Sir4p-dependent pathway. Mol Microbiol 55:1259–1271

    PubMed  CAS  Google Scholar 

  68. 68.

    De Las Peñas A, Pan SJ, Castaño I, Alder J, Cregg R, Cormack BP (2003) Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev 17:2245–2258

    Google Scholar 

  69. 69.

    Cormack BP, Ghori N, Falkow S (1999) An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells. Science 285:578–582

    PubMed  CAS  Google Scholar 

  70. 70.

    Silva S, Henriques M, Oliveira R, Williams D, Azeredo J (2010) In vitro biofilm activity of non-Candida albicans Candida species. Curr Microbiol 61:534–540. doi:10.1007/s00284-010-9649-7

    PubMed  CAS  Google Scholar 

  71. 71.

    van Dyk D, Pretorius IS, Bauer FF (2005) Mss11p is a central element of the regulatory network that controls FLO11 expression and invasive growth in Saccharomyces cerevisiae. Genetics 169:91–106

    PubMed Central  PubMed  Google Scholar 

  72. 72.

    Riera M, Mogensen E, d’Enfert C, Janbon G (2012) New regulators of biofilm development in Candida glabrata. Res Microbiol 163:297–307

    PubMed  CAS  Google Scholar 

  73. 73.

    Guo B, Styles CA, Feng Q, Fink GR (2000) A Saccharomyces gene family involved in invasive growth, cell–cell adhesion, and mating. Proc Natl Acad Sci U S A 97:12158–12163

    PubMed Central  PubMed  CAS  Google Scholar 

  74. 74.

    Sheppard DC, Yeaman MR, Welch WH et al (2004) Functional and structural diversity in the Als protein family of Candida albicans. J Biol Chem 279:30480–30489

    PubMed  CAS  Google Scholar 

  75. 75.

    Caudle KE, Barker KS, Wiederhold NP, Xu L, Homayouni R, Rogers PD (2011) Genomewide expression profile analysis of the Candida glabrata Pdr1 regulon. Eukaryot Cell 10(3):373–383. doi:10.1128/EC.00073-10

    PubMed Central  PubMed  CAS  Google Scholar 

  76. 76.

    Gutiérrez-Escribano P, Zeidler U, Suárez MB et al (2012) The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans. PLoS Pathog 8(5):e1002683. doi:10.1371/journal.ppat.1002683

    PubMed Central  PubMed  Google Scholar 

  77. 77.

    Chakrabarti A, Nayak N, Talwar P (1991) In vitro proteinase production by Candida species. Mycopathologia 114:163–168

    PubMed  CAS  Google Scholar 

  78. 78.

    Marcos-Arias C, Eraso E, Madariaga L, Aguirre JM, Quindós G (2011) Phospholipase and proteinase activities of Candida isolates from denture wearers. Mycoses 54(4):e10–e16. doi:10.1111/j.1439-0507.2009.01812.x

    PubMed  Google Scholar 

  79. 79.

    Mohan das V, Ballal M (2008) Proteinase and phospholipase activity as virulence factors in Candida species isolated from blood. Rev Iberoam Micol 25(4):208–210

    PubMed  Google Scholar 

  80. 80.

    Kalkanci A, Güzel AB, Khalil II, Aydin M, Ilkit M, Kuştimur S (2012) Yeast vaginitis during pregnancy: susceptibility testing of 13 antifungal drugs and boric acid and the detection of four virulence factors. Med Mycol 50(6):585–593. doi:10.3109/13693786.2012.662597

    PubMed  CAS  Google Scholar 

  81. 81.

    Ueno K, Matsumoto Y, Uno J et al (2011) Intestinal resident yeast Candida glabrata requires Cyb2p-mediated lactate assimilation to adapt in mouse intestine. PLoS One 6(9):e24759

    PubMed Central  PubMed  CAS  Google Scholar 

  82. 82.

    Sikora M, Dabkowska M, Swoboda-Kopec E et al (2011) Differences in proteolytic activity and gene profiles of fungal strains isolated from the total parenteral nutrition patients. Folia Microbiol (Praha) 56(2):143–148. doi:10.1007/s12223-011-0023-3

    CAS  Google Scholar 

  83. 83.

    Negri M, Martins M, Henriques M et al (2010) Examination of potential virulence factors of Candida tropicalis clinical isolates from hospitalized patients. Mycophatologia 169:175–182. doi:10.1007/s11046-009-9246-0

    CAS  Google Scholar 

  84. 84.

    Luo G, Samaranayake LP (2002) Candida glabrata, an emerging fungal pathogen, exhibits superior relative cell surface hydrophobicity and adhesion to denture acrylic surfaces compared with Candida albicans. APMIS 110:601–610

    PubMed  CAS  Google Scholar 

  85. 85.

    Luo G, Samaranayake LP, Cheung BP, Tang G (2004) Reverse transcriptase polymerase chain reaction (RT-PCR) detection of HLP gene expression in Candida glabrata and its possible role in in vitro haemolysin production. APMIS 112:283–290

    PubMed  CAS  Google Scholar 

  86. 86.

    Berila N, Hyroššová P, Subík J (2011) Oxidative stress response and virulence factors in Candida glabrata clinical isolates. Folia Microbiol (Praha) 56(2):116–121. doi:10.1007/s12223-011-0016-2

    CAS  Google Scholar 

  87. 87.

    Bader O, Schwarz A, Kraneveld EA et al (2012) Gross karyotypic and phenotypic alterations among different progenies of the Candida glabrata CBS138/ATCC2001 reference strain. PLoS One 7(12):e52218. doi:10.1371/journal.pone.0052218

    PubMed Central  PubMed  CAS  Google Scholar 

  88. 88.

    Rai MN, Balusu S, Gorityala N, Dandu L, Kaur R (2012) Functional genomic analysis of Candida glabrata–macrophage interaction: role of chromatin remodeling in virulence. PLoS Pathog 8(8):e1002863. doi:10.1371/journal.ppat.1002863

    PubMed Central  PubMed  CAS  Google Scholar 

  89. 89.

    Niimi M, Firth NA, Cannon RD (2010) Antifungal drug resistance of oral fungi. Odontology 98(1):15–25

    PubMed  CAS  Google Scholar 

  90. 90.

    Akins RA (2005) An update on antifungal targets and mechanisms of resistance in Candida albicans. Med Mycol 43(4):285–318

    PubMed  CAS  Google Scholar 

  91. 91.

    Van Bambeke F, Balzi E, Tulkens PM (2000) Antibiotic efflux pumps. Biochem Pharmacol 60(4):457–470

    PubMed  Google Scholar 

  92. 92.

    Wilson D, Thewes S, Zakikhany K et al (2009) Identifying infection-associated genes of Candida albicans in the postgenomic era. FEMS Yeast Res 9:688–700

    PubMed  CAS  Google Scholar 

  93. 93.

    Brunke S, Seider K, Almeida RS et al (2010) Candida glabrata tryptophan-based pigment production via the Ehrlich pathway. Mol Microbiol 76:25–47

    PubMed  CAS  Google Scholar 

  94. 94.

    Tscherner M, Schwarzmüller T, Kuchler K (2011) Pathogenesis and antifungal drug resistance of the human fungal pathogen Candida glabrata. Pharmaceuticals 4:169–186. doi:10.3390/ph4010169

    Google Scholar 

  95. 95.

    Henry KW, Nickels JT, Edlind TD (2000) Upregulation of ERG genes in Candida species by azoles and other sterol biosynthesis inhibitors. Antimicrob Agents Chemother 44(10):2693–2700

    PubMed Central  PubMed  CAS  Google Scholar 

  96. 96.

    Stead DA, Walker J, Holcombe L et al (2009) Impact of the transcriptional regulator, Ace2, on the Candida glabrata secretome. Proteomics 10:212–223

    Google Scholar 

  97. 97.

    Calcagno AM, Bignell E, Warn P et al (2003) Candida glabrata STE12 is required for wild-type levels of virulence and nitrogen starvation induced filamentation. Mol Microbiol 50:1309–1318

    PubMed  CAS  Google Scholar 

  98. 98.

    Ferrari S, Sanguinetti M, De Bernardis F et al (2011) Loss of mitochondrial functions associated with azole resistance in Candida glabrata results in enhanced virulence in mice. Antimicrob Agents Chemother 55:1852–1860

    PubMed Central  PubMed  CAS  Google Scholar 

  99. 99.

    Kaur R, Castaño I, Cormack BP (2004) Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Antimicrob Agents Chemother 48:1600–1613

    PubMed Central  PubMed  CAS  Google Scholar 

  100. 100.

    Miyazaki T, Yamauchi S, Inamine T et al (2010) Roles of calcineurin and crz1 in antifungal susceptibility and virulence of Candida glabrata. Antimicrob Agents Chemother 54:1639–1643

    PubMed Central  PubMed  CAS  Google Scholar 

  101. 101.

    Bennett JE, Izumikawa K, Marr KA (2004) Mechanism of increased fluconazole resistance in Candida glabrata during prophylaxis. Antimicrob Agents Chemother 48:1773–1777

    PubMed Central  PubMed  CAS  Google Scholar 

  102. 102.

    Noble JA, Tsai HF, Suffis SD, Su Q, Myers TG, Bennett JE (2013) STB5 Is a negative regulator of azole resistance in Candida glabrata. Antimicrob Agents Chemother 57(2):959–967. doi:10.1128/AAC.01278-12

    PubMed Central  PubMed  CAS  Google Scholar 

  103. 103.

    Vermitsky JP, Edlind TD (2004) Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-Like transcription factor. Antimicrob Agents Chemother 48:3773–3781

    PubMed Central  PubMed  CAS  Google Scholar 

  104. 104.

    Vale-Silva L, Ischer F, LeibundGut-Landmann S, Sanglard D (2013) Gain-of-function mutations in PDR1, a regulator of antifungal drug resistance in Candida glabrata, control adherence to host cells. Infect Immun 81(5):1709–1720. doi:10.1128/IAI.00074-13

    PubMed Central  PubMed  CAS  Google Scholar 

  105. 105.

    Paul S, Schmidt JA, Moye-Rowley WS (2011) Regulation of the CgPdr1 transcription factor from the pathogen Candida glabrata. Eukaryot Cell 10(2):187–197

    PubMed Central  PubMed  CAS  Google Scholar 

  106. 106.

    Ferrari S, Sanguinetti M, Torelli R, Posteraro B, Sanglard D (2011) Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata. PLoS One 6(3):e17589. doi:10.1371/journal.pone.0017589

    PubMed Central  PubMed  CAS  Google Scholar 

  107. 107.

    Chen KH, Miyazaki T, Tsai HF, Bennett JE (2007) The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Gene 386(1–2):63–72

    PubMed  CAS  Google Scholar 

  108. 108.

    Farahyar S, Zaini F, Kordbacheh P et al (2013) Overexpression of aldo-keto-reductase in azole-resistant clinical isolates of Candida glabrata determined by cDNA-AFLP. Daru 21:1

    PubMed Central  PubMed  CAS  Google Scholar 

  109. 109.

    Thompson GR 3rd, Wiederhold NP, Vallor AC, Villareal NC, Lewis JS 2nd, Patterson TF (2008) Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother 52:3783–3785

    PubMed Central  PubMed  CAS  Google Scholar 

  110. 110.

    Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Messer SA, Jones RN (2012) Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J Clin Microbiol 50:1199–1203

    PubMed Central  PubMed  CAS  Google Scholar 

  111. 111.

    Arendrup MC, Perlin DS, Jensen RH, Howard SJ, Goodwin J, Hope W (2012) Differential in vivo activities of anidulafungin, caspofungin, and micafungin against Candida glabrata isolates with and without FKS resistance mutations. Antimicrob Agents Chemother 56:2435–2442

    PubMed Central  PubMed  CAS  Google Scholar 

  112. 112.

    Shields RK, Nguyen MH, Press EG et al (2012) The presence of an FKS mutation rather than MIC is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to Candida glabrata. Antimicrob Agents Chemother 56:4862–4869

    PubMed Central  PubMed  CAS  Google Scholar 

  113. 113.

    Alexander BD, Johnson MD, Pfeiffer CD et al (2013) Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis 56(12):1724–1732

    PubMed  Google Scholar 

  114. 114.

    Vandeputte P, Tronchin G, Larcher G et al (2008) A nonsense mutation in the ERG6 gene leads to reduced susceptibility to polyenes in a clinical isolate of Candida glabrata. Antimicrob Agents Chemother 52:3701–3709

    PubMed Central  PubMed  CAS  Google Scholar 

  115. 115.

    Vandeputte P, Tronchin G, Bergès T, Hennequin C, Chabasse D, Bouchara JP (2007) Reduced susceptibility to polyenes associated with a missense mutation in the erg6 gene in a clinical isolate of Candida glabrata with pseudohyphal growth. Antimicrob Agents Chemother 51:982–990

    PubMed Central  PubMed  CAS  Google Scholar 

  116. 116.

    Helmerhorst EJ, Venuleo C, Sanglard D, Oppenheim FG (2006) Roles of cellular respiration, CgCDR1, and CgCDR2 in Candida glabrata resistance to histatin 5. Antimicrob Agents Chemother 50:1100–1103

    PubMed Central  PubMed  CAS  Google Scholar 

  117. 117.

    Edgerton M, Koshlukova SE (2000) Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva. Adv Dent Res 14:16–21

    PubMed  CAS  Google Scholar 

  118. 118.

    Helmerhorst EJ, Oppenheim FG (2004) The antifungal mechanisms of antimicrobial proteins. In: Hancock REW, Devine D (eds) Mammalian antimicrobial proteins, 1st edn. Cambridge University Press, Cambridge, pp 245–277

    Google Scholar 

  119. 119.

    Oppenheim FG (1989) Salivary histidine-rich proteins. In: Tenovuo JO (ed) Human saliva: clinical chemistry and microbiology. CRC Press, Boca Raton, pp 151–160

    Google Scholar 

  120. 120.

    Oppenheim FG, Xu T, McMillian FM et al (1988) Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J Biol Chem 263:7472–7477

    PubMed  CAS  Google Scholar 

  121. 121.

    Tsai H, Bobek LA (1998) Human salivary histatins: promising anti-fungal therapeutic agents. Crit Rev Oral Biol Med 9:480–497

    PubMed  CAS  Google Scholar 

  122. 122.

    Van Urk H, Voll WSL, Scheffers WA, van Dijken JP (1990) Transient-state analysis of metabolic fluxes in Crabtree-positive and Crabtree-negative yeasts. Appl Environ Microbiol 56:281–287

    PubMed Central  PubMed  Google Scholar 

  123. 123.

    Niimi M, Kamiyama A, Tokunaga M (1988) Respiration of medically important Candida species and Saccharomyces cerevisiae in relation to glucose effect. J Med Vet Mycol 26:195–198

    PubMed  CAS  Google Scholar 

  124. 124.

    Shahi P, Moye-Rowley WS (2009) Coordinate control of lipid composition and drug transport activities is required for normal multidrug resistance in fungi. Biochim Biophys Acta 1794:852–859

    PubMed Central  PubMed  CAS  Google Scholar 

  125. 125.

    Muller H, Thierry A, Coppée JY et al (2009) Genomic polymorphism in the population of Candida glabrata: Gene copy-number variation and chromosomal translocations. Fungal Genet Biol 46:264–276

    PubMed  CAS  Google Scholar 

  126. 126.

    Thierry A, Bouchier C, Dujon B, Richard GF (2008) Megasatellites: a peculiar class of giant minisatellites in genes involved in cell adhesion and pathogenicity in Candida glabrata. Nucleic Acids Res 36(18):5970–5982

    PubMed Central  PubMed  CAS  Google Scholar 

  127. 127.

    Barchiesi F, Falconi Di Francesco L, Arzeni D, Caselli F, Gallo D, Scalise G (1999) Electrophoretic karyotyping and triazole susceptibility of Candida glabrata clinical isolates. Eur J Clin Microbiol Infect Dis 18:184–187

    PubMed  CAS  Google Scholar 

  128. 128.

    Kaufmann CS, Merz WG (1989) Electrophoretic karyotypes of Torulopsis glabrata. J Clin Microbiol 27:2165–2168

    PubMed Central  PubMed  CAS  Google Scholar 

  129. 129.

    Klempp-Selb B, Rimek D, Kappe R (2000) Karyotyping of Candida albicans and Candida glabrata from patients with Candida sepsis. Mycoses 43:159–163

    PubMed  CAS  Google Scholar 

  130. 130.

    Lin CY, Chen YC, Lo HJ, Chen KW, Li SY (2007) Assessment of Candida glabrata strain relatedness by pulsed-field gel electrophoresis and multilocus sequence typing. J Clin Microbiol 45:2452–2459

    PubMed Central  PubMed  CAS  Google Scholar 

  131. 131.

    Shin JH, Chae MJ, Song JW et al (2007) Changes in karyotype and azole susceptibility of sequential bloodstream isolates from patients with Candida glabrata candidemia. J Clin Microbiol 45:2385–2391

    PubMed Central  PubMed  CAS  Google Scholar 

  132. 132.

    Magee BB, Sanchez MD, Saunders D, Harris D, Berriman M, Magee PT (2008) Extensive chromosome rearrangements distinguish the karyotype of the hypovirulent species Candida dubliniensis from the virulent Candida albicans. Fungal Genet Biol 45:338–350

    PubMed Central  PubMed  CAS  Google Scholar 

  133. 133.

    Samaranayake LP (1990) Host factors and oral candidosis. In: Samaranayake LP, MacFarlane TW (eds) Oral candidosis. Wright-Butterworth, London, pp 66–103

    Google Scholar 

  134. 134.

    Hawser SP, Baillie GS, Douglas LJ (1998) Production of extracellular matrix by Candida albicans biofilms. J Med Microbiol 47(3):253–256

    PubMed  CAS  Google Scholar 

  135. 135.

    Chandra J, Mukherjee PK, Leidich SD et al (2001) Antifungal resistance of candidal biofilms formed on denture acrylic in vitro. J Dent Res 80(3):903–908

    PubMed  CAS  Google Scholar 

  136. 136.

    Al-Fattani MA, Douglas LJ (2004) Penetration of Candida biofilms by antifungal agents. Antimicrob Agents Chemother 48(9):3291–3297

    PubMed Central  PubMed  CAS  Google Scholar 

  137. 137.

    Blankenship JR, Mitchell AP (2006) How to build a biofilm: a fungal perspective. Curr Opin Microbiol 9(6):588–594

    PubMed  CAS  Google Scholar 

  138. 138.

    Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA (2001) Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183(18):5385–5394

    PubMed Central  PubMed  CAS  Google Scholar 

  139. 139.

    Ramage G, Vande Walle K, Wickes BL, López-Ribot JL (2001) Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother 45(9):2475–2479

    PubMed Central  PubMed  CAS  Google Scholar 

  140. 140.

    Hawser S (1996) Adhesion of different Candida spp. to plastic: XTT formazan determinations. J Med Vet Mycol 34(6):407–410

    PubMed  CAS  Google Scholar 

  141. 141.

    Mah TFC, O’Toole GA (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 9:34–39

    PubMed  CAS  Google Scholar 

  142. 142.

    Uppuluri P, Chaturvedi AK, Srinivasan A et al (2010) Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog 6(3):e1000828

    PubMed Central  PubMed  Google Scholar 

  143. 143.

    Perumal P, Mekala S, Chaffin WL (2007) Role for cell density in antifungal drug resistance in Candida albicans biofilms. Antimicrob Agents Chemother 51(7):2454–2463

    PubMed Central  PubMed  CAS  Google Scholar 

  144. 144.

    Ramage G, Rajendran R, Sherry L, Williams C (2012) Fungal biofilm resistance. Int J Microbiol 2012:528521. doi:10.1155/2012/528521

    PubMed Central  PubMed  Google Scholar 

  145. 145.

    Bandara HM, Lam OL, Watt RM, Jin LJ, Samaranayake LP (2010) Bacterial lipopolysaccharides variably modulate in vitro biofilm formation of Candida species. J Med Microbiol 59(Pt 10):1225–1234. doi:10.1099/jmm.0.021832-0

    PubMed  CAS  Google Scholar 

  146. 146.

    Halliwell SC, Smith MCA, Muston P, Holland SL, Avery SV (2012) Heterogeneous expression of the virulence-related adhesin Epa1 between individual cells and strains of the pathogen Candida glabrata. Eukaryot Cell 11(2):141–150

    PubMed Central  PubMed  CAS  Google Scholar 

  147. 147.

    Taff HT, Nett JE, Zarnowski R et al (2012) A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog 8(8):e1002848. doi:10.1371/journal.ppat.1002848

    PubMed Central  PubMed  CAS  Google Scholar 

  148. 148.

    Cannon RD, Lamping E, Holmes AR et al (2007) Candida albicans drug resistance—another way to cope with stress. Microbiology 153(Pt 10):3211–3217

    PubMed  CAS  Google Scholar 

  149. 149.

    Seneviratne CJ, Wang Y, Jin L, Abiko Y, Samaranayake LP (2010) Proteomics of drug resistance in Candida glabrata biofilms. Proteomics 10:1444–1454

    PubMed  CAS  Google Scholar 

  150. 150.

    LaFleur MD, Kumamoto CA, Lewis K (2006) Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob Agents Chemother 50(11):3839–3846

    PubMed Central  PubMed  CAS  Google Scholar 

  151. 151.

    Lewis K (2008) Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol 322:107–131

    PubMed  CAS  Google Scholar 

  152. 152.

    Lewis K (2010) Persister cells. Annu Rev Microbiol 64:357–372

    PubMed  CAS  Google Scholar 

  153. 153.

    Lafleur MD, Qi Q, Lewis K (2010) Patients with long-term oral carriage harbor high-persister mutants of Candida albicans”. Antimicrob Agents Chemother 54(1):39–44

    PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Célia F. Rodrigues’ grant.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to M. Henriques.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rodrigues, C.F., Silva, S. & Henriques, M. Candida glabrata: a review of its features and resistance. Eur J Clin Microbiol Infect Dis 33, 673–688 (2014). https://doi.org/10.1007/s10096-013-2009-3

Download citation

Keywords

  • Fluconazole
  • Azole
  • Ergosterol
  • Candida Species
  • Micafungin