A conserved regulator controls asexual sporulation in the fungal pathogen Candida albicans

Abstract

Transcription factor Rme1 is conserved among ascomycetes and regulates meiosis and pseudohyphal growth in Saccharomyces cerevisiae. The genome of the meiosis-defective pathogen Candida albicans encodes an Rme1 homolog that is part of a transcriptional circuitry controlling hyphal growth. Here, we use chromatin immunoprecipitation and genome-wide expression analyses to study a possible role of Rme1 in C. albicans morphogenesis. We find that Rme1 binds upstream and activates the expression of genes that are upregulated during chlamydosporulation, an asexual process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolishes chlamydosporulation in three Candida species, whereas its overexpression bypasses the requirement for chlamydosporulation cues and regulators. RME1 expression levels correlate with chlamydosporulation efficiency across clinical isolates. Interestingly, RME1 displays a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase dependent on Rme1 function and independent of chlamydospore-inducing cues. Our results indicate that Rme1 plays a central role in chlamydospore development in Candida species.

A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Candida Chlamydospore Cell Wall

“…The fluorescent signal was not observed on hyphal cells, consistent with the presence of chitosan specifically in the chlamydospore wall. Similar staining of C. albicans chlamydospores with Eosin Y has recently been reported ( 45 ).…”

“…In S. cerevisiae , the Srt1 and Rrt8/Lds1/Lds2 proteins are localized to lipid droplets, and lipid droplets are associated with the forming spore wall, suggesting some connection between lipid droplets and the assembly of the outer spore wall layers ( 34 – 36 ). C. albicans chlamydospores are reported to be rich in neutral lipids and lipid droplets based on both biochemical fractionation and staining with a lipid droplet dye ( 45 , 54 ). To examine lipid droplets in C. dubliniensis chlamydospores, the cells were stained with the lipid droplet dye monodansylpentane (MDH) ( 55 ).…”

Overexpression approaches to advance understanding of Candida albicans

“…An overexpression study of RME1 , a zinc finger transcription factor identified its role during C. albicans chlamydospore formation. Indeed, overexpression of RME1 led to the up‐regulation of chlamydospore‐related genes, and to the binding of a TAP‐tagged Rme1 at the promoters of these target genes (Hernandez‐Cervantes et al., 2020 ). Subsequent examination of the phenotype of the overexpressing strain in chlamydospore‐inducing conditions confirmed Rme1 involvement in the process, allowing a bypass of environmental cues and regulators that are required for chlamydospore formation (Hernandez‐Cervantes et al., 2020 ).…”

“…Indeed, overexpression of RME1 led to the up‐regulation of chlamydospore‐related genes, and to the binding of a TAP‐tagged Rme1 at the promoters of these target genes (Hernandez‐Cervantes et al., 2020 ). Subsequent examination of the phenotype of the overexpressing strain in chlamydospore‐inducing conditions confirmed Rme1 involvement in the process, allowing a bypass of environmental cues and regulators that are required for chlamydospore formation (Hernandez‐Cervantes et al., 2020 ). As in the previous study, the knockout mutant showed the opposite phenotype, that is, the absence of chlamydospore formation, even in favorable conditions.…”

Secondary Metabolism Gene Clusters Exhibit Increasingly Dynamic and Differential Expression during Asexual Growth, Conidiation, and Sexual Development in Neurospora crassa

“…However, environmental factors, including nutrients, are also key regulators for development and reproduction in many fungi. Genes regulating sporulation are known to affect some SMCs ( 48 – 51 ). Therefore, investigation of the expression of SMCs across fungal development in additional environmental contexts provides an opportunity to enhance our understanding of their regulation and function.…”