Differential expression of the NRG1 repressor controls species-specific regulation of chlamydospore development in Candida albicans and Candida dubliniensis.

Candida albicans and Candida dubliniensis are opportunistic fungal pathogens that are closely related but differ in their epidemiology and in some phenotypic characteristics, including certain virulence-related traits. A comparison of these two species at the molecular level could therefore provide new insights into the biology and pathogenicity of Candida. Both species share the ability to produce chlamydospores, but only C. dubliniensis forms pseudohyphae with abundant chlamydospores on Staib agar (syn. Guizotia abyssinica creatinine agar), on which C. albicans grows as a budding yeast. To understand the basis of this species-specific, differential regulation of morphogenetic development, we set out to identify C. albicans genes that repress chlamydospore formation under these conditions. A C. albicans genomic library was integrated into the C. dubliniensis genome and transformants were screened for clones in which filamentation and/or chlamydospore production on Staib agar was suppressed. This screen identified two genes, CaNRG1 and CaPDE2, encoding a general transcriptional repressor and a high affinity cAMP phosphodiesterase, respectively. Expression of CaNRG1 in C. dubliniensis repressed pseudohyphae and chlamydospore formation, whereas expression of CaPDE2 only reduced the extent of filamentous growth but did not affect chlamydospore formation. We found that C. dubliniensis, but not C. albicans, specifically downregulates NRG1 expression on Staib medium to allow chlamydospore development. Artificial overexpression of CdNRG1 suppressed pseudohyphal growth and production of chlamydospores in C. dubliniensis. Conversely, deletion of CaNRG1 in C. albicans resulted in chlamydospore formation on Staib agar, confirming its central role in the regulation of this morphogenetic process. Our results demonstrate that differential regulation of a single gene, NRG1, in C. albicans and C. dubliniensis is responsible for their species-specific response to environmental signals that induce chlamydospore development.