Candida nivariensis, an emerging pathogenic fungus with multidrug resistance to antifungal agents

Abstract

In 2005, Candida nivariensis, a yeast species genetically related to Candida glabrata, was described following its isolation from three patients in a single Spanish hospital. Between 2005 and 2006, 16 fungal isolates with phenotypic similarities to C. nivariensis were submitted to the United Kingdom Mycology Reference Laboratory for identification. The strains originated from various clinical specimens, including deep, usually sterile sites, from patients at 12 different hospitals in the United Kingdom. PCR amplification and sequencing of the D1D2 and internal transcribed spacer 1 (ITS1) regions of the nuclear ribosomal gene cassette confirmed that these isolates from the United Kingdom are genetically identical to C. nivariensis. Biochemically, C. glabrata and C. nivariensis are distinguished by their differential abilities to assimilate trehalose. However, in contrast to the original published findings, we found that C. glabrata isolates, but not C. nivariensis isolates, are capable of assimilating this substrate. Antifungal susceptibility tests revealed that C. nivariensis isolates are less susceptible than C. glabrata isolates to itraconazole, fluconazole, and voriconazole and to have significantly higher flucytosine MICs than C. glabrata strains. Finally, C. nivariensis could be rapidly distinguished from the other common pathogenic fungus species by pyrosequencing of the ITS2 region. In the light of these data, we believe that C. nivariensis should be regarded as a clinically important emerging pathogenic fungus.

FIG. 1.

Phylogenetic analysis of the LSU (A) and ITS1 (B) data sets. Unrooted neighbor-joining consensus trees are drawn. Bootstrap values above 50% are indicated. The EMBL accession and NCPF numbers are listed in Table 1. The sequences with EMBL accession numbers AY627305, AY927306, and AY627307 correspond to the D1D2 sequences of the three original C. nivariensis isolates described previously (1), and EMBL accession numbers AY620957, AY620958, and AY620959 correspond to the ITS1 sequences of the three original C. nivariensis isolates described previously (1). EMBL accession number AF313362 corresponds to the D1D2 sequence of a potential C. nivariensis isolate from flowers in Canada (11).