Fluconazole‐Resistant Pathogens Candida inconspicua and C. norvegensis: DNA Sequence Diversity of the rRNA Intergenic Spacer Region, Antifungal Drug Susceptibility, and Extracellular Enzyme Production

Abstract

The opportunistic fungal pathogens Candida inconspicua and C. norvegensis are very rarely isolated from patients and are resistant to fluconazole. We collected 38 strains of the two microorganisms isolated from Europe and Japan, and compared the polymorphism of the rRNA intergenic spacer (IGS) and internal transcribed spacer (ITS) regions, antifungal drug susceptibility, and extracellular enzyme production as a potential virulence factor. While the IGS sequences of C. norvegensis were not very divergent (more than 96.7% sequence similarity among the strains), those of C. inconspicua showed remarkable diversity, and were divided into four genotypes with three subtypes. In the ITS region, no variation was found in either species. Since the sequence similarity of the two species is approximately 70% at the ITS region, they are closely related phylogenetically. Fluconazole resistance was reconfirmed for the two microorganisms but they were susceptible to micafungin and amphotericin B. No strain of either species secreted aspartyl proteinase or phospholipase B. These results provide basal information for accurate identification, which is of benefit to global molecular epidemiological studies and facilitates our understanding of the medical mycological characteristics of C. inconspicua and C. norvegensis.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

“…inconspicua and C. norvegensis are both similar phenotypically to C. krusei (141,173,284). Like C. krusei, they exhibit intrinsic resistance to fluconazole (15,50,142,143,221,257,284). C. inconspicua has been reported to be a cause of fungemia in human immunodeficiency virus-infected patients and in patients with hematologic malignancies (15,50).…”

“…norvegensis has been reported from clinical specimens in Norway, The Netherlands, and Japan (284). Although most isolates to date have been from respiratory specimens, Sandven and colleagues (257,259) have identified this species from blood, urine, and peritoneal fluid.…”

Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-Year Analysis of Susceptibilities of Candida Species to Fluconazole and Voriconazole as Determined by CLSI Standardized Disk Diffusion

“…norvegensis has been isolated from the oropharynx, blood, peritoneal fluid, urine, and a variety of deep tissue sites (22,39,40,62,67). As with C. inconspicua, C. norvegensis was isolated most frequently from the respiratory tract and with approximately equal frequency from the other specimen types (Table 9).…”

Phylogenetic Relationships Matter: Antifungal Susceptibility among Clinically Relevant Yeasts

“…In practice, the terms anamorph and teleomorph have been dropped in favor of the terms asexual stage and sexual stage, and all legitimate names proposed for a species, regardless of which reproduction stage they are typified by, can serve as the correct name for that species (5,6,9). The usage of molecular tools has led to the recognition of many novel polymorphic and cryptic species (two or more distinct species classified as a single species) and species complexes, e.g., in Candida parapsilosis, Candida guilliermondii, Candida glabrata, and Aspergillus niger (10)(11)(12)(13)(14)(15)(16)(17). To avoid uncertainties caused by frequent renaming and reassigning of human-pathogenic fungi, a plea with the aim of uncoupling molecular phylogeny from nomenclature was published by de Hoog et al (18).…”