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

Abstract

Candida dubliniensis is closely related to Candida albicans, a major causative agent of candidiasis, and is primarily associated with oral colonization and infection in human immunodeficiency virus (HIV)-positive patients. Despite the high similarity of genomic and phenotypic features between the 2 species, C. dubliniensis is much less virulent and less prevalent than C. albicans. The ability to change morphological phenotypes is a striking feature of Candida species and is linked to virulence. In this study, we report a novel phenotype, the gray phenotype, in C. dubliniensis. Together with the previously reported white and opaque cell types, the gray phenotype forms a tristable phenotypic switching system in C. dubliniensis that is similar to the white-gray-opaque tristable switching system in C. albicans. Gray cells of C. dubliniensis are similar to their counterparts in C. albicans in terms of several biological aspects including cellular morphology, mating competence, and genetic regulatory mechanisms. However, the gray phenotypes of the 2 species have some distinguishing features. For example, the secreted aspartyl protease (Sap) activity is induced by bovine serum albumin (BSA) in gray cells of C. albicans, but not in gray cells of C. dubliniensis. Taken together, our results demonstrate that the biological features and regulatory mechanisms of white-gray-opaque tristable transitions are largely conserved in the 2 pathogenic Candida species.

Gray phenotype: Enhanced fitness strategy for Candida dubliniensis?

“…Yue H. et al 6 also report that at least 9 genes involved in ergosterol biosynthesis and 3 mannanbiosyntesisrelated genes were up-regulated in gray cells of C. dubliniensis. These genes play a critical role in the regulation of antifungal resistance and other stresses.…”

“…While in-depth mechanisms relating the gray phenotype to the biology and pathogenicity of C. dubliniensis are awaiting further studies, this report by Yue H. et al 6 recalls our attention to C. dubliniensis as a special pathogen in search for a specific place in the biology and pathogenicity of Candida species and its separation from C. albicans.…”

“…Yue H. et al 6 show that while the gray phenotype of C. dubliniensis is fostered by the combined use of N-Acetylglucosammine (GlcNAc) and CO 2 while the opaque phenotype is favored in C. albicans under the above conditions. Given that commensal bacteria release in the oral cavity GlcNAc and CO 2 , the switch to the gray phenotype could help C. dubliniensis to compete with bacterial members and C. albicans itself, for colonizing this preferred biological niche.…”

“…8 Gray cells of C. dubliniensis are similar to their counterparts in C. albicans in terms of several biological aspects including cellular morphology, mating competence and genetic regulatory mechanisms. 6 However, the gray phenotypes of the 2 species have some distinguishing features which may contribute to explain the colonization of a specific oral niche by C. dubliniensis and conversely the easier adaptation of C. albicans to most host tissues.…”

“…[3][4][5] No surprise, the high genetic similarity between C. albicans and C. dubliniensis anticipated a similar phenotypic switch phenomenon in the latter, that in fact has now been described by Yue H. et al in this issue of Virulence. 6 In this Editorial, we will focus on the possible role of gray phenotype of C. dubliniensis as a new strategy of this fungus to survive, grow and manifest its virulence in selected host niche, comparing it with the gray cells of C. albicans. The possible role of gray cells of C. dubliniensis as a mechanism evolved by this fungus to escape immune response at mucosal surfaces and grow undisturbed in the oral cavity of HIV-positive patients is discussed.…”