The HOG MAPK pathway in Candida albicans: more than an osmosensing pathway
- 31 Downloads
In 1993, Brewster and Gustin described the existence of a kinase whose activity was essential for Saccharomyces cerevisiae to grow in environments with high osmolarity. This led to the discovery of the HOG pathway, a MAP kinase (MAPK) pathway that has been revealed to be crucial to respond to a wide range of stress conditions frequently encountered by fungi in their common habitats. MAPK signaling is initiated at the plasma membrane, where triggering stimuli lead to a phosphorylation cascade that ultimately activates transcription factors to ensure an appropriate adaptive response. In pathogenic fungi, the HOG pathway gains special significance as it is involved in traits related to pathogenicity; these include biofilm formation, adhesion to surfaces, and morphogenetic and epigenetic transitions. It also plays a role in controlling both the pathogen and the commensal state program. Understanding the signals leading to its activation, the elements of the pathways and the targets of the pathway are therefore of primary importance in the design of novel antifungals.
KeywordsHOG MAPK Candida albicans Stress Fungi
Work in our laboratory is supported by the Spanish Ministerio de Economía y Competitividad under Grant BIO2015-64777-P and by Comunidad de Madrid under InGEMICS-CM S2017/BMD3691 (Group COMIPAT).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Alonso-Monge R et al (1999) Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol 181:3058–3068Google Scholar
- Arana DM, Alonso-Monge R, Du C, Calderone R, Pla J (2007) Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans. Cell Microbiol 9:1647–1659. https://doi.org/10.1111/j.1462-5822.2007.00898.x CrossRefGoogle Scholar
- Cruz MC, Sia RA, Olson M, Cox GM, Heitman J (2000) Comparison of the roles of calcineurin in physiology and virulence in serotype D and serotype A strains of Cryptococcus neoformans Infect Immun 68: 982–985Google Scholar
- de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3: 735–740Google Scholar
- Ene IV, Lohse MB, Vladu AV, Morschhauser J, Johnson AD, Bennett RJ (2016) Phenotypic profiling reveals that Candida albicans opaque cells represent a metabolically specialized cell state compared to default white cells MBio 7 doi: https://doi.org/10.1128/mBio.01269-16
- Hagiwara D, Takahashi-Nakaguchi A, Toyotome T, Yoshimi A, Abe K, Kamei K, Gonoi T, Kawamoto S (2013) NikA/TcsC histidine kinase is involved in conidiation, hyphal morphology, and responses to osmotic stress and antifungal chemicals in Aspergillus fumigatus. PLoS One 8:e80881. https://doi.org/10.1371/journal.pone.0080881 CrossRefGoogle Scholar
- Herrero de Dios C, Román E, Diez C, Alonso-Monge R, Pla J (2013) The transmembrane protein Opy2 mediates activation of the Cek1 MAP kinase in Candida albicans. Fungal Genet Biol 50: 21–32Google Scholar
- Herrero-de-Dios C, Day AM, Tillmann AT, Kastora SL, Stead D, Salgado PS, Quinn J, Brown AJP (2018) Redox regulation, rather than stress-induced phosphorylation, of a Hog1 mitogen-activated protein kinase modulates its nitrosative-stress-specific outputs. MBio 9:e02229–e02217. https://doi.org/10.1128/mBio.02229-17 CrossRefGoogle Scholar
- Herskowitz (1995) MAP kinase pathways in yeast: for mating and more. Cell 80: 187–197Google Scholar
- Homman S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiolo Mol Biol Rev 66: 300–372Google Scholar
- Huang X, Chen X, He Y, Yu X, Li S, Gao N, Niu L, Mao Y, Wang Y, Wu X, Wu W, Wu J, Zhou D, Zhan X, Chen C (2017) Mitochondrial complex I bridges a connection between regulation of carbon flexibility and gastrointestinal commensalism in the human fungal pathogen Candida albicans. PLoS Pathog 13:e1006414. https://doi.org/10.1371/journal.ppat.1006414 CrossRefGoogle Scholar
- Kultz D (1998) Phylogenetic and functional classification of mitogen- and stress-activated protein kinases. J MolEvol 46:571–588Google Scholar
- Munro CA, Selvaggini S, de Bruijin I, Walker L, Lenardon MD, Gerssen B, Milne S, Brown AJ, Gow NA (2007) The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol Microbiol 63: 1399–1413Google Scholar
- Posas F, Chambers JR, Heyman JA, Hoeffler JP, de Nadal E, Ariño J (2000) The transcriptional response of yeast to saline stress. J Biol Chem 275: 17249–17255Google Scholar
- Rep M, Proft M, Remize F, Tamas M, Serrano R, Thevelein JM, Hohmann S (2001) The Saccharomyces cerevisiae Sko1p transcription factor mediates HOG pathway-dependent osmotic regulation of a set of genes encoding enzymes implicated in protection from oxidative damage. Mol Microbiol 40:1067–1083CrossRefGoogle Scholar
- Sonneborn A, Bockmuhl DP, Ernst JF (1999) Chlamydospore formation in Candida albicans requires the Efg1p morphogenetic regulator. Infect Immun 67:5514–5517Google Scholar