Candida

Recently, several taxonomic rearrangements have been made and many well-known Candida species have been renamed and moved to other genera, notably Pichia kudriavzevii (formerly Candida krusei), Meyerozyma guilliermondii (formerly Candida guilliermondii), Clavispora lusitaniae (formerly Candida lusitaniae), Kluyveromyces marxianus (formerly Candida kefyr), Diutina catenulata (formerly Candida catenulata), Diutina rugosa (formerly Candida rugosa) and Wickerhamomyces anomalus (formerly Candida pelliculosa). C. glabrata and C. parapsilosis are now recognised as species complexes (Tavanti 2005; Correia 2006; Alcoba-Florez 2005).

Candida microscopy

Candida albicans showing typical cream-coloured, smooth surfaced, waxy colonies and narrow based budding spherical to ovoid blastoconidia.

The genus Candida is characterised by globose to elongate yeast-like cells or blastoconidia that reproduce by narrow-based multilateral budding. Pseudohyphae and occasionally true hyphae may also be present. Colony pigmentation is usually absent. Ballistoconidia are not formed. Arthroconidia may be formed, but not extensively. Sexual reproduction is absent. Glucose may be fermented. Nitrate may be assimilated. Starch-like compounds are not produced. The diazonium blue B reaction is negative. The genus is highly polyphyletic, as it comprises mitosporic species that are devoid of special distinguishing features (Lachance et al. 2011).

Several species may be aetiological agents, most commonly Candida albicans, followed by C. parapsilosis, C. glabrata, C. tropicalis and Pichia kudriavzevii. Altogether, these five species account for >95% of human infections. However a number of other species may also be isolated. All are ubiquitous and occur naturally on humans.

Species descriptions

  • Candida albicans

    Candida albicans is a commensal of mucous membranes and the gastrointestinal tract. Environmental isolations have been made from sources contaminated by human or animal excreta, such as polluted water, soil, air and plants.

    RG-2 organism.

    Culture: 
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy: 
    Spherical to subspherical budding blastoconidia, 2-7 x 3-8 µm in size.

    India ink preparation: 
    Negative - no capsules present.

    Dalmau plate culture:
    Branched pseudohyphae with dense verticils of blastoconidia. Spherical chlamydospores, mostly terminal, often on a slightly swollen subtending cell, are formed near the edge of the cover slip.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube + L-Sorbose v L-Arabinose v D-Glucitol v
    Fermentation   Sucrose v D-Arabinose v 𝝰-M-D-Glucoside v
    Glucose + Maltose + D-Ribose v D-Gluconate v
    Galactose v Cellobiose - L-Rhamnose - DL-Lactate +
    Sucrose v Trehalose v D-Glucosamime v myo-Inositol -
    Maltose + Lactose - N-A-D-glucosamine v 2-K-D-Gluconate +
    Lactose - Melibiose - Glycerol v D-Glucuronate -
    Trehalose v Raffinose - Erythritol - Nitrate -
    Assimilation   Melezitose v Ribitol v Urease -
    Glucose + Soluble Starch + Galactitol - 0.1% Cycloheximide +
    Galactose + D-Xylose + D-Mannitol + Growth at 40C +

    Key features: 
    Germ tube positive, production of chlamydospores on Dalmau plate culture, fermentation of glucose, sugar assimilation profile and a distinctive green colour on CHROMagar. Note: Germ tube negative variants (previously known as C. claussenii), and sucrose-negative variants (previously described as C. stellatoidea) may occur.

    Antifungal susceptibility: Candida albicans (Australian national data); MIC µg/mL.
    Antifungal No ≤0.008 0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 2438   2 16 162 648 785 785 199 2          
    FLU 2443   2 2 3 91 744 1039 369 77 18 16 28 14 40
    ISAV 646 261 333 46 2 1 1 1         1    
    VORI 2169 1168 598 204 82 28 26 24 11 9 1 2 6    
    POSA 1810 102 688 717 186 59 28 16 12 1   1      
    ITRA 2443 20 140 707 1013 431 54 43 14 3   1 17    
    ANID 1537 5 469 596 347 112 6 1   1          
    MICA 1535 858 570 90 12 4   1              
    CAS 1865 3 27 381 878 434 124 17 1            
    5FC 2443 4   147 1137 517 241 249 86 20 10 7 3 3 19

     

  • Candida auris

    Candida auris is an emerging multidrug-resistant yeast that causes invasive infections, that was first described in 2009 in Japan and has since been reported from several countries (Lockhart et al. CID 2017:64)

    Candida auris is now a notifiable condition under the South Australian public health regulations.

    RG-2 organism.

    Culture:
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy:
    Spherical to subspherical budding blastoconidia, 2-3 x 2-5 µm in size.

    India ink preparation:
    Negative - no capsules present.

    Dalmau plate culture:
    Ovoid budding yeast cells only. No pseudohyphae produced.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube - L-Sorbose - L-Arabinose - D-Glucitol +
    Fermentation   Sucrose + D-Arabinose - 𝝰-M-D-glucoside -
    Glucose + Maltose + D-Ribose - D-Gluconate -
    Galactose - Cellobiose - L-Rhamnose - DL-Lactate -
    Sucrose w,+ Trehalose + D-Glucosamine - myo-Inositol -
    Maltose - Lactose - NAD-glucosamine - 2-K-D-Gluconate +
    Lactose - Melibiose - Glycerol - D-Glucuronate -
    Trehalose w,+ Raffinose + Erythritol - Nitrate -
    Assimilation   Melezitose + Ribitol w,+ Urease -
    Glucose + Soluble Starch + Galactitol + 0.1% Cycloheximide -
    Galactose - D-Xylose - D-Mannitol + Growth at 42C +

    Key features:
    C. auris is difficult to identify with standard laboratory methods such API or VITEK-2, and has been misidentified as Candida haemulonis or Saccharomyces cerevisiae. Current identification methods are MALDI-ToF or D1/D2 and ITS sequencing.

    Antifungal susceptibility: Candida auris very limited data (Australian national data); MIC µg/mL.
    Antifungal No ≤0.008 0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 6               1 2 3        
    FLU 6                       1 1 4
    VORI 6       1   1   3 1          
    POSA 6 1 1   1 1 2                
    ITRA 6   1   1   2 2              
    ANID 6         3   1     1        
    MICA 6       1 2   1       2      
    CAS 6         3   1   1 1        
    5FC 6       4 2                  
  • Candida dubliniensis

    Candida dubliniensis is an occasional cause of candidaemia and mucosal infection, especially in HIV patients.

    RG-2 organism.

    Culture:
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy:
    Spherical to subspherical budding blastoconidia, 3-8 x 2-7 µm in size.

    India ink preparation:
    Negative - no capsules present.

    Dalmau plate culture:
    Branched pseudohyphae with dense verticils of blastoconidia and spherical, mostly terminal chlamydospores.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube + L-Sorbose - L-Arabinose - D-Glucitol +
    Fermentation   Sucrose + D-Arabinose - 𝝰-M-D-glucoside +,s
    Glucose + Maltose + D-Ribose - D-Gluconate -
    Galactose +,s Cellobiose - L-Rhamnose - DL-Lactate +
    Sucrose - Trehalose s,+ D-Glucosamine v myo-Inositol -
    Maltose + Lactose - NAD-glucosamine + 2-K-D-Gluconate +
    Lactose - Melibiose - Glycerol w,s,+ D-Glucuronate -
    Trehalose v Raffinose - Erythritol - Nitrate -
    Assimilation   Melezitose w,+ Ribitol + Urease -
    Glucose + Soluble Starch w,+ Galactitol - 0.1% Cycloheximide +
    Galactose + D-Xylose s,+ D-Mannitol + Growth at 40C +  

    Key features:
    Germ tube positive, similar to C. albicans, except for absence of growth at 42C; glycerol (mostly +), methyl-a-D-glucoside (-), trehalose (-), and D-xylose (-). Initial colonies dark green on CHROMagar and producing rough colonies on bird seed agar. ITS sequencing and MALDI-TOF can reliably distinguish C. dubliniensis from C. albicans.

     

    Antifungal susceptibility: Candida dubliniensis (Australian national data); MIC µg/mL.
    Antifungal No ≤0.008 0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 165   1 1 3 35 71 49 5            
    FLU 165         72 63 25 5            
    ISAV 28 14 9 4 1                    
    VORI 162 152 10                        
    POSA 149 35 47 48 16 3                  
    ITRA 165 6 62 43 42 8 4                
    ANID 140 1 18 32 39 40 3         6      
    MICA 140 6 61 54 10 2           6      
    CAS 155     10 74 51 10 1   1   7      
    5FC 165     12 131 15 4 2   1          
  • Candida glabrata complex

    Recently Candida glabrata has been recognised as a species complex consisting of C. glabrata, C. bracarensis (Correia et al. 2006) and C. nivariensis (Alcoba-Flórez et al. 2005).

    These three species are phenotypically indistinguishable and are best identified by molecular methods. C. bracarensis was described based on PCR-fingerprints and sequence divergence in the D1/D2 domains (Correia et al. 2006). C. nivariensis was differentiated from other yeasts on the basis of ITS sequences (Borman et al. 2008).

    Candida glabrata Candida bracarensis  Candida nivariensis

  • Candida haemulonii complex

    Candida haemulonii has recently been reclassified as a complex of three phenotypically identical but genotypically distinct entities: C. haemulonii, C. duobushaemulonii and C. haemulonii var. vulnera, based on ITS and D1/D2 sequencing (Cendejas-Bueno et al. 2012, Ramos et al. 2015).

    Candida haemulonii

    RG-1 organism.

    Culture: 
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy: 
    Ovoid to globose, budding yeast-like cells or blastoconidia, 2-7 x 2-7 µm. No pseudohyphae produced.

    India ink preparation: 
    Negative - no capsules present.

    Dalmau plate culture: 
    No pseudohyphae produced.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube - L-Sorbose - L-Arabinose - D-Glucitol +
    Fermentation   Sucrose + D-Arabinose -- 𝝰-M-D-Glucoside -
    Glucose + Maltose + D-Ribose - D-Gluconate +
    Galactose - Cellobiose - L-Rhamnose +,w DL-Lactate -
    Sucrose - Trehalose + D-Glucosamime +,s myo-Inositol -
    Maltose - Lactose - N-A-D-glucosamine + 2-K-D-Gluconate +
    Lactose - Melibiose - Glycerol +,s D-Glucuronate -
    Trehalose +,s Raffinose +,s Erythritol - Nitrate -
    Assimilation   Melezitose +,w Ribitol +,s Urease -
    Glucose + Soluble Starch - Galactitol - 0.1% Cycloheximide -
    Galactose +,w D-Xylose - D-Mannitol + Growth at 37C -

    Key features: Germ tube negative yeast and sugar assimilation pattern. Molecular identification may be required. C. haemulonii has been reported from a few cases of fungaemia but clinical isolations remain rare.

    Antifungal susceptibility: Candida haemulonii (Australian national data); MIC µg/mL.
    Antifungal No ≤0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 30         2 10 7 7 1 2      
    FLU 30           1   3 1       25
    VORI 28   1 1   1 1       20 4    
    POSA 23 1 2   1         1 3 16    
    ITRA 30   2 1 2     1       24    
    ANID 21   13 1 3 1       1   2    
    MICA 21   2 10 3 2           4    
    CAS 28     1 2 4 6       1 14    
    5FC 25   2 4 7 6 2 3 1          
  • Candida inconspicua

    Candida inconspicua is a rare cause of candidaemia.

    RG-2 organism.

    Culture: 
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy: 
    Ellipsoidal budding blastoconidia, 3-5 x 1.8-3 µm in size. No pseudohyphae or chlamydospores produced.

    India ink preparation: 
    Negative - no capsules present.

    Dalmau plate culture: 
    No pseudohyphae produced.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube - L-Sorbose - L-Arabinose - D-Glucitol -
    Fermentation   Sucrose   D-Arabinose - 𝝰-M-D-Glucoside -
    Glucose + Maltose - D-Ribose - D-Gluconate -
    Galactose - Cellobiose - L-Rhamnose - DL-Lactate +
    Sucrose - Trehalose - D-Glucosamime + myo-Inositol -
    Maltose - Lactose - N-A-D-glucosamine + 2-K-D-Gluconate -
    Lactose - Melibiose - Glycerol + D-Glucuronate -
    Trehalose - Raffinose - Erythritol - Nitrate -
    Assimilation   Melezitose - Ribitol - Urease -
    Glucose + Soluble Starch - Galactitol - 0.1% Cycloheximide -
    Galactose - D-Xylose - D-Mannitol - Growth at 40C +

    Key features:
    Germ tube negative yeast and sugar assimilation pattern and colonies are white on Candida CHROMagar.

    Antifungal susceptibility: Candida inconspicua (Australian national data); MIC µg/mL.
    Antifungal No ≤0.008 0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 16 2 2 1 1 3 6 1              
    FLU 16                       2 4 10
    VORI 13       2 4 3 2 1            
    POSA 13       2 3 5 2       1      
    ITRA 15         2 6 6 1            
    ANID 2   2                        
    MICA 2   2                        
    CAS 13       2 5 5   1            
    5FC 14         1   1 2 4 3 1 1 1  
  • Candida parapsilosis complex

    Recently Candida parapsilosis has been recognised as a complex of four species: C. parapsilosis, C. orthopsilosis, C. metapsilosis and Lodderomyces elongisporus (Tavanti et al. 2005).

    These four species are phenotypically indistinguishable and are best identified by ITS sequencing or MALDI-TOF MS analysis.

    Candida parapsilosis Candida metapsilosis Candida orthopsilosis

  • Candida tropicalis

    Candida tropicalis is a major cause of septicaemia and disseminated candidiasis. It is also found as part of the normal human mucocutaneous flora and environmental isolations have been made from faeces, shrimp, kefir and soil.

    RG-2 organism.

    Culture: 
    Colonies (SDA) white to cream-coloured smooth, glabrous, yeast-like.

    Microscopy: 
    Spherical to subspherical budding yeast-like cells or blastoconidia, 3.5-7 x 5.5-10 µm.

    India ink preparation: 
    Negative - no capsules present.

    Dalmau plate culture:
    Abundant, long, wavy, branched pseudohyphae with numerous ovoid blastoconidia, budding off. Terminal vesicles (chlamydospores) are not produced.

    Physiological Tests: + Positive, - Negative, v Variable, w Weak, s Slow, nd No Data
    Germ Tube - L-Sorbose v L-Arabinose - D-Glucitol +
    Fermentation   Sucrose v D-Arabinose - 𝝰-M-D-Glucoside v
    Glucose + Maltose + D-Ribose v,s D-Gluconate v
    Galactose + Cellobiose v L-Rhamnose - DL-Lactate v
    Sucrose v Trehalose + D-Glucosamime v myo-Inositol -
    Maltose + Lactose - N-A-D-glucosamine + 2-K-D-Gluconate +
    Lactose - Melibiose - Glycerol v D-Glucuronate -
    Trehalose +,s Raffinose - Erythritol - Nitrate -
    Assimilation   Melezitose v Ribitol v Urease -
    Glucose + Soluble Starch + Galactitol - 0.1% Cycloheximide +
    Galactose + D-Xylose + D-Mannitol + Growth at 40C +

    Key features:
    Germ tube negative yeast and sugar assimilation pattern. Colonies are dark blue on Candida CHROMagar.

    Antifungal susceptibility: Candida tropicalis (Australian national data); MIC µg/mL.
    Antifungal No ≤0.008 0.016 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 ≥64
    AMB 336       5 41 72 107 106 4 1        
    FLU 336         1 9 51 122 81 36 14 4 5 13
    ISAV 148 1 10 45 50 23 10 5 2 1 1        
    VORI 303 8 14 41 78 84 45 13 5 9 1 4 1    
    POSA 284 1 7 25 53 95 68 19 9 2   5      
    ITRA 336   2 12 20 134 118 36 3 2 1 1 7    
    ANID 230   10 10 35 152 20 2     1 1      
    MICA 230 8 38 154 24 3 1 1     1 1      
    CAS 279   2 14 109 90 47 10 3     3 1    
    5FC 336     31 205 58 21 5 2 1 1 2 1 2 7