The two‐component response regulator Skn7 belongs to a network of transcription factors regulating morphogenesis in Candida albicans and independently limits morphogenesis‐induced ROS accumulation

Abstract

Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) in filament-inducing conditions on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.

Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space

“…It also included the induction of positive regulators of filamentation such as HWP1 , HGC1 , UME6 and BRG1 , and downregulation of the negative regulator of filamentation NRG1 ( Fig 7E and 7F ) . Finally, the HSF1 overexpression-specific targets encompassed genes known to be regulated by other morphogenetic regulators including the heat shock factor (HSF)-type transcription factors Sfl2 and Skn7[ 45 , 46 ]. These Hsf1-dependent morphogenetic regulators are ideal candidates for targets through which HSF1 overexpression could induce morphogenesis.…”

Antiaging of Cucurbitane Glycosides from Fruits of Momordica charantia L.

“…UTH1 gene essentially takes part in oxidative stress regulation, and deletion of UTH1 gene will lead to extend the replicative lifespan of yeast [ 25 ]. SKN7 is upstream gene and is a stress response transcription factor in Saccharomyces cerevisiae [ 26 ]. Superoxide dismutases (SOD) are major ROS scavenging enzymes and can convert superoxide anion to hydrogen peroxide [ 24 ].…”

The regulation of hyphae growth in Candida albicans

“…Skn7 is a conservative fungal heat shock factor-type transcriptional regulator that is part of a two-component signal transduction system. Previous studies have also revealed a close functional interaction between Skn7 and major morphogenetic regulators (including Efg1, Cph1, and Ume6), suggesting that Skn7 is part of the transcriptional pathway that controls filamentous growth of C. albicans [106].…”