A Novel Function for Hog1 Stress-Activated Protein Kinase in Controlling White-Opaque Switching and Mating in Candida albicans

Abstract

Candida albicans is a commensal in heathy people but has the potential to become an opportunistic pathogen and is responsible for half of all clinical infections in immunocompromised patients. Central to understanding C. albicans behavior is the whiteopaque phenotypic switch, in which cells can undergo an epigenetic transition between the white state and the opaque state. The phenotypic switch regulates multiple properties, including biofilm formation, virulence, mating, and fungus-host interactions. Switching between the white and opaque states is associated with many external stimuli, such as oxidative stress, pH, and N-acetylglucosamine, and is directly regulated by the Wor1 transcriptional circuit. The Hog1 stress-activated protein kinase (SAPK) pathway is recognized as the main pathway for adapting to environmental stress in C. albicans. In this work, we first show that loss of the HOG1 gene in a/a and ␣/␣ cells, but not a/␣ cells, results in 100% white-to-opaque switching when cells are grown on synthetic medium, indicating that switching is repressed by the a1/␣2 heterodimer that represses WOR1 gene expression. Indeed, switching in the hog1⌬ strain was dependent on the presence of WOR1, as a hog1⌬ wor1⌬ strain did not show switching to the opaque state. Deletion of PBS2 and SSK2 also resulted in C. albicans cells switching from white to opaque with 100% efficiency, indicating that the entire Hog1 SAPK pathway is involved in regulating this unique phenotypic transition. Interestingly, all Hog1 pathway mutants also caused defects in shmoo formation and mating efficiencies. Overall, this work reveals a novel role for the Hog1 SAPK pathway in regulating white-opaque switching and sexual behavior in C. albicans.

Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence

“…Besides its role in the regulation of hyperosmotic stress, the S. cerevisiae Hog1 pathway has also been shown as associated to other stresses (Rodrígues‐Peña et al ., 2010), such as oxidative stress (Bilsland et al ., ), acid stress (Lawrence et al ., , Mollapour and Piper, ), methylglyoxal (Aguilera et al ., ), temperature downshift (Panadero et al ., 2006), arsenite (Thorsen et al ., ), cesium chloride (Del Vescovo et al ., ), heat shock (Winkler et al ., ) and zymolyase (Bermejo et al ., ) . In other fungi, the multifunctional role of the orthologous HOG pathway is also observed, such as Candida albicans where Hog1 is involved in numerous stress responses including osmotic, oxidative, iron, cell wall, ergosterol, in addition to white‐opaque switching and mating (Kaba et al ., ; Thomas et al ., ; Liang et al ., ; Komalapriya et al ., ; Ene et al ., ).…”

SPT20 Regulates the Hog1-MAPK Pathway and Is Involved in Candida albicans Response to Hyperosmotic Stress

“…We thank Ching-Hsuan Lin for providing the C. albicans hog1 / mutant strain and the hog1 /HOG1 strain (Liang et al, 2014), Aaron P. Mitchell for providing plasmid pCJN542, and Eishi Noguchi for providing plasmid pFA6a-5FLAG-KanMX6 (Addgene plasmid # 15983).…”

White-opaque Switching in Different Mating Type-like Locus Gene Types of Clinical Candida albicans Isolates

“…We will clarify why the isolates from China occurred significantly WO transition. Furthermore, the mechanism of WO switching in MTL a/α isolates has not been clearly explained yet, although stress-activated protein kinase pathway and WOR 1 gene have been reported to play roles in the process of switching,[17] further investigations are still needed.…”