Dataset Information

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.

SUBMITTER: Yang D

PROVIDER: S-EPMC7022667 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Yang Dongliang D Hu Yanling Y Yin Zixin Z Gao Qianru Q Zhang Yuqian Y Chan Fong Yee FY Zeng Guisheng G Weng Lixing L Wang Lianhui L Wang Yue Y

Microorganisms 20200103 1

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 pre ...[more]

PMID: 31947778

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Project description:Sfl1p and Sfl2p are two homologous heat shock factor-type transcriptional regulators that antagonistically control morphogenesis in Candida albicans, while being required for full pathogenesis and virulence. To understand how Sfl1p and Sfl2p exert their function, we combined genome-wide location and expression analyses to reveal their transcriptional targets in vivo together with the associated changes of the C. albicans transcriptome. We show that Sfl1p and Sfl2p bind to the promoter of at least 113 common targets through divergent binding motifs and modulate directly the expression of key transcriptional regulators of C. albicans morphogenesis and/or virulence. Surprisingly, we found that Sfl2p additionally binds to the promoter of 75 specific targets, including a high proportion of hyphal-specific genes (HSGs; HWP1, HYR1, ECE1, others), revealing a direct link between Sfl2p and hyphal development. Data mining pointed to a regulatory network in which Sfl1p and Sfl2p act as both transcriptional activators and repressors. Sfl1p directly represses the expression of positive regulators of hyphal growth (BRG1, UME6, TEC1, SFL2), while upregulating both yeast form-associated genes (RME1, RHD1, YWP1) and repressors of morphogenesis (SSN6, NRG1). On the other hand, Sfl2p directly upregulates HSGs and activators of hyphal growth (UME6, TEC1), while downregulating yeast form-associated genes and repressors of morphogenesis (NRG1, RFG1, SFL1). Using genetic interaction analyses, we provide further evidences that Sfl1p and Sfl2p antagonistically control C. albicans morphogenesis through direct modulation of the expression of important regulators of hyphal growth. Bioinformatic analyses suggest that binding of Sfl1p and Sfl2p to their targets occurs with the co-binding of Efg1p and/or Ndt80p. We show, indeed, that Sfl1p and Sfl2p targets are bound by Efg1p and that both Sfl1p and Sfl2p associate in vivo with Efg1p. Taken together, our data suggest that Sfl1p and Sfl2p act as central "switch on/off" proteins to coordinate the regulation of C. albicans morphogenesis.

Dataset Information

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

Publications

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

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