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Characterization of a Candida albicans Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network

1
iBiMED-Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal
2
Medical Research Council Centre for Medical Mycology, School of Biosciences, University of Exeter, Exeter EX4 4QD, UK
3
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knoell-Institute, Beutenbergstraße 11A, 07745 Jena, Germany
4
Institute of Microbiology, Friedrich Schiller University, Neugasse 25, 07743 Jena, Germany
5
Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Avda. Ramón y Cajal s/n, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
J. Fungi 2020, 6(4), 230; https://doi.org/10.3390/jof6040230
Received: 15 September 2020 / Revised: 12 October 2020 / Accepted: 14 October 2020 / Published: 17 October 2020
(This article belongs to the Special Issue Cell Wall Stress Response)
The success of Candida albicans as a pathogen relies on its ability to adapt and proliferate in different environmental niches. Pathways regulated by mitogen-activated protein kinases (MAPKs) are involved in sensing environmental conditions and developing an accurate adaptive response. Given the frequent cooperative roles of these routes in cellular functions, we have generated mutants defective in all combinations of the four described MAPKs in C. albicans and characterized its phenotype regarding sensitiveness to specific drugs, morphogenesis and interaction with host immune cells. We demonstrate that all MAPKs are dispensable in this yeast as a mutant defective in Cek1, Cek2, Mkc1 and Hog1 is viable although highly sensitive to oxidative and osmotic stress, displaying a specific pattern of sensitivity to antifungals. By comparing its phenotype with single, double and triple combinations of MAPK-deletion mutants we were able to unveil a Cek1-independent mechanism for Hog1 resistance to Congo red, and confirm the predominant effect of Hog1 on oxidative and osmotic adaptation. The quadruple mutant produces filaments under non-inducing conditions, but is unable to develop chlamydospores. Furthermore, cek1 cek2 mkc1 hog1 cells switch to the opaque state at high frequency, which is blocked by the ectopic expression of HOG1 suggesting a role of this kinase for phenotypic switching. View Full-Text
Keywords: MAPK; osmotic stress; filamentation; chlamydospore; cell wall; oxidative stress; fungal virulence MAPK; osmotic stress; filamentation; chlamydospore; cell wall; oxidative stress; fungal virulence
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Correia, I.; Wilson, D.; Hube, B.; Pla, J. Characterization of a Candida albicans Mutant Defective in All MAPKs Highlights the Major Role of Hog1 in the MAPK Signaling Network. J. Fungi 2020, 6, 230.

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