The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans.
Candida albicans mutants with mutations in mitogen-activated protein (MAP) kinase HOG1 displayed an increased sensitivity to agents producing reactive oxygen species, such as oxidants (menadione, hydrogen peroxide, or potassium superoxide), and UV light. Consistent with this finding, C. albicans Hog1 was activated not only in response to an increase in external osmolarity, as happens with its Saccharomyces cerevisiae homologue, but also in response to hydrogen peroxide. The Hog1-mediated response to oxidative stress was different from that of transcription factor Cap1, the homologue of S. cerevisiae Yap1, as shown by the different sensitivities to oxidants and the kinetics of cell death of cap1Delta, hog1, and hog1 cap1Delta mutants. Deletion of CAP1 did not influence the level of Hog1 phosphorylation, and deletion of HOG1 did not affect Cap1 nuclear localization. Moreover, we show that the HOG1 gene plays a role in chlamydospore formation, another oxygen-related morphogenetic event, as demonstrated by the fact that hog1 cells were unable to generate these thick-walled structures in several media through a mechanism different from that of the EFG1 regulator. This is the first demonstration of the role of the Hog1-mediated MAP kinase pathway in resistance to oxidative stress in pathogenic fungi, and it allows us to propose a molecular model for the oxidative stress response in C. albicans.
Alonso-Monge
Rebeca
R
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, E-28040 Madrid, Spain.
Navarro-García
Federico
F
Román
Elvira
E
Negredo
Ana I
AI
Eisman
Blanca
B
Nombela
César
C
Pla
Jesús
J
D050976:Basic-Leucine Zipper Transcription Factors; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005656:Fungal Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D015388:Organelles / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D009994:Osmolar Concentration; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000378:metabolism*; D014466:Ultraviolet Rays
D050976:Basic-Leucine Zipper Transcription Factors; C426523:CAP1 protein, Candida albicans; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases