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.
Highlights
Candida albicans is a prevalent opportunistic fungal pathogen that is frequently observed in the mucosal surfaces of healthy individuals [1]
Our previous study indicated that C. albicans filament formation is more effectively inhibited by exogenous addition of BDSF than farnesol in glucose minimum medium (GMM) containing 20% filtered fetal bovine serum (FBS) or RPMI 1640 supplemented with 4-morpholinepropanesulfonic acid [32,33]
C. albicans remains the main species of Candida bloodstream infections [28,34]
Summary
Candida albicans is a prevalent opportunistic fungal pathogen that is frequently observed in the mucosal surfaces of healthy individuals [1]. Among the virulence traits of C. albicans, the ability to switch growth forms between yeast, pseudohyphae, and hyphae is critically important [9]. This phenotypic plasticity is governed by many different environmental cues, including pH, temperature, nutrient availability, and the presence of chemicals that stimulate or repress the filamentation pathway [10,11]. Cis-2-dodecenoic acid (BDSF) is a farnesol analogue that has been shown to be more effective in inhibiting C. albicans hyphal formation. It can be extracted from Burkholderia cenocepacia metabolite but not from C. albicans [13–15]
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