The Closely Related Species Candida albicans and Candida dubliniensis Can Mate

Abstract

Because Candida dubliniensis is closely related to Candida albicans, we tested whether it underwent whiteopaque switching and mating and whether white-opaque switching depended on MTL homozygosity and mating depended on switching, as they do in C. albicans. We also tested whether C. dubliniensis could mate with C. albicans. Sequencing revealed that the MTL␣ locus of C. dubliniensis was highly similar to that of C. albicans. Hybridization with the MTLa1, MTLa2, MTL␣1, and MTL␣2 open reading frames of C. albicans further revealed that, as in C. albicans, natural strains of C. dubliniensis exist as a/␣, a/a, and ␣/␣, but the proportion of MTL homozygotes is 33%, 10 times the frequency of natural C. albicans strains. C. dubliniensis underwent white-opaque switching, and, as in C. albicans, the switching was dependent on MTL homozygosis. C. dubliniensis a/a and ␣/␣ cells also mated, and, as in C. albicans, mating was dependent on a switch from white to opaque. However, white-opaque switching occurred at unusually high frequencies, opaque cell growth was frequently aberrant, and white-opaque switching in many strains was camouflaged by an additional switching system. Mating of C. dubliniensis was far less frequent in suspension cultures, due to the absence of matingdependent clumping. Mating did occur, however, at higher frequencies on agar or on the skin of newborn mice. The increases in MTL homozygosity, the increase in switching frequencies, the decrease in the quality of switching, and the decrease in mating efficiency all reflected a general deterioration in the regulation of developmental processes, very probably due to the very high frequency of recombination and genomic reorganization characteristic of C. dubliniensis. Finally, interspecies mating readily occurred between opaque C. dubliniensis and C. albicans strains of opposite mating type in suspension, on agar, and on mouse skin. Remarkably, the efficiency of interspecies mating was higher than intraspecies C. dubliniensis mating, and interspecies karyogamy occurred readily with apparently the same sequence of nuclear migration, fusion, and division steps observed during intraspecies C. albicans and C. dubliniensis mating and Saccharomyces cerevisiae mating.Beginning in 1990, a number of studies of the genetic relatedness of Candida albicans isolates derived from human immunodeficiency virus (HIV)-positive individuals identified atypical strains (9,29,31,33,49). These strains were subsequently grouped into the separate species C. dubliniensis in 1995 by Coleman, Sullivan, and coworkers (52). This new species shared a number of phenotypic characteristics with C. albicans, including two that in the past had been used to distinguish C. albicans from other species, namely, chlamydospore and true hypha formation (52). Like C. albicans, C. dubliniensis was diploid, contained a homolog to the dispersed complex repeat sequence RPS, and underwent the bud-hypha transition and colony-based 3153A-like phenotypic switching (10,17,19,37,50,51). The basic phenotypic char...

Discovery of the gray phenotype and white-gray-opaque tristable phenotypic transitions inCandida dubliniensis

“…White-opaque switching was not observed in d163 in a previous study. 13 The discrepancy between our findings and the previous study could be due to the use of different media and culture conditions. Of note, d163 (a/a), P86 (a/a), and PC35 (a/a) are homozygous at the mating type locus (MTL), which controls white-opaque switching in C. albicans.…”

“…d163, P86, and d172 were isolated from HIV-infected patients, and PC35 was from a healthy individual. 13 To verify that these strains were in fact C. dubliniensis, we sequenced the internal transcribed spacer (ITS) region of the rRNA genes. The colony and cellular morphology of the gray cells of all 3 C. dubliniensis strains was similar to that of C. albicans gray cells ( Fig.…”

“…It has been reported that 3 Candida species (C. albicans, C.dubliniensis, and C. tropicalis) can undergo white-opaque switching, which is linked to the ability to cause systemic and cutaneous infections and to undergo sexual mating. 13,[19][20][21]25,34,35 We have recently discovered that C. albicans can also exist as a novel cell type, the gray phenotype, 25 which is distinct from the well-studied white and opaque cell types. 21 In the current study, we report the discovery of the gray phenotype and white-gray-opaque transitions in C. dubliniensis.…”

“…13,26,34,35 Opaque cells mate much more efficiently than white cells in these species. We tested the mating competence of white, gray, and opaque cells of C. dubliniensis.…”

“…3,11,12 Epidemiological studies indicate that C. dubliniensis is primarily associated with human immunodeficiency virus (HIV)-infected patients. [6][7][8][9] A number of comparative genomic and phenotypic studies of C. albicans and C. dubliniensis have been performed in the previous 2 decades, [12][13][14][15] but what underlying mechanisms or biological characteristics underlying the differences between the 2 species in epidemiology, virulence, and the ability to develop antifungal resistance remain to be investigated.…”