Candida albicans Ubiquitin and Heat Shock Factor-Type Transcriptional Factors Are Involved in 2-Dodecenoic Acid-Mediated Inhibition of Hyphal Growth

Abstract

Cis-2-dodecenoic acid (i.e., Burkholderia cenocepacia Diffusible Signal Factor, BDSF), a signaling molecule produced by Burkholderia cenocepacia but not by Candida albicans, can prevent Candida albicans hyphal formation. The mechanism by which BDSF controls the morphological switch of C. albicans is still unknown. To address this issue, we used the cDNA microarray method to investigate the differential expression of genes in C. albicans in the presence and absence of BDSF. The microarray result indicated that 305 genes were significantly different in the expression level. This included the downregulation of 75 genes and the upregulation of 230 genes. Based on the microarray data, a mutant library was screened to search for genes, once mutated, conferred insensitivity to BDSF. The results showed that the repressors (Ubi4 and Sfl1 proteins) and the activator (Sfl2 protein) of filamentous growth are involved in the BDSF regulation of hyphal morphogenesis. Ubi4, an ubiquitin polypeptide that participates in ubiquitin-mediated protein turnover, is the protein required for the degradation of Sfl2. Sfl1 and Sfl2 proteins antagonistically control C. albicans morphogenesis. In the hyphal induction condition, the amount of Ubi4 and Sfl1 protein increased rapidly with the exogenous addition of BDSF. As a result, the protein level of the activator of filamentous growth, Sfl2, decreased correspondingly, thereby facilitating the C. albicans cells to remain in the yeast form.

From Jekyll to Hyde: The Yeast–Hyphal Transition of Candida albicans

“…DSF released by S. maltophilia has been reported to interfere with two key virulence factors of C. albicans : the yeast-to-hyphae transition and biofilm formation [ 96 ]. Recent microarray studies revealed the involvement of repressors (Ubi4 and Sfl1) and the activator (Sfl2) of filamentous growth in BDSF regulation of hyphal morphogenesis [ 97 ]. With the addition of BDSF, elevated levels of Ubi4 and Sfl1 and degradation of Sfl2 block the yeast-to-hyphae transition.…”

Multi-omics approaches to understand pathogenicity during potato early blight disease caused by Alternaria solani

“…These substances attached to C88 leaf cells to promote TA-0410 infection and colonization. In fungal pathogens, ubiquitin genes had been shown to play important roles in fungal development, stress resistance, and fungal virulence ( Chen et al, 2018 ; Yang et al, 2020 ; Cao and Xue, 2021 ). Transcription factors (TFs) regulate different aspects of fungal development and virulence ( Shelest, 2008 ; John et al, 2021 ).…”

“…These results can be further utilized in the analysis of genome remodeling and pathogenesis of the A. solani . Ubiquitin system had been also shown to play important roles in fungal development, stress resistance and fungal virulence ( Chen et al, 2018 ; Yang et al, 2020 ; Cao and Xue, 2021 ). Thus, the ubiquitin-proteasome system related gene in A. solani found in this article may plays an important role in virulence.…”

More Than Just Cleaning: Ubiquitin-Mediated Proteolysis in Fungal Pathogenesis

“…The polyubiquitin gene UBI4 contains three ubiquitin repeats and is involved in fungal growth and virulence ( Sepulveda et al., 1996 ; Leach et al., 2011 ). Deletion of UBI4 in C. albicans induces morphological transition from yeast to hyphae, which is important for the pathogenicity of C. albicans ( Roig and Gozalbo, 2003 ; Yang D. et al., 2020 ). The ubi4 ∆/∆ mutant displays a cell wall biosynthesis defect when exposed to a number of cell wall stresses including treatment with the anti-fungal drug caspofungin ( Leach et al., 2011 ).…”