The HOG MAPK pathway in Candida albicans: more than an osmosensing pathway

  1. Román González, Elvira 1
  2. Correia, Inês 2
  3. Prieto Prieto, Antonio Daniel 1
  4. Alonso Monge, Rebeca María Mar 1
  5. Pla Alonso, Jesús 1
  1. 1 Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040, Madrid, Spain
  2. 2 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208 |, 4200-135, Porto, Portugal
Revista:
International Microbiology

ISSN: 1139-6709,  1618-1905

Año de publicación: 2019

Volumen: 23

Número: 1

Páginas: 23-29

Tipo: Artículo

DOI: 10.1007/S10123-019-00069-1 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: International Microbiology

Resumen

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.

€ Ver financiación

Información de financiación

Financiadores

  • MINECO
    • BIO2015-64777-P
  • InGEMICS-CM
    • BMD3691

Referencias bibliográficas

  • Alonso-Monge R et al (1999) Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol 181:3058–3068
  • Alonso-Monge R, Navarro-Garcia F, Roman E, Negredo AI, Eisman B, Nombela C, Pla J (2003) The Hog1 mitogen-activated protein kinase is essential in the oxidative stress response and chlamydospore formation in Candida albicans. Eukaryot Cell 2:351–361
  • Alonso-Monge R, Román E, Arana DM, Prieto AD, Urrialde V, Nombela C, Pla J (2010) The Sko1 protein represses the yeast-to-hypha transition and regulates the oxidative stress response in Candida albicans. Fungal Genet Biol 47:587–601
  • 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
  • Arana DM, Nombela C, Alonso-Monge R, Pla J (2005) The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology 151:1033–1049. https://doi.org/10.1099/mic.0.27723-0
  • Bahn YS, Kojima K, Cox GM, Heitman J (2005) Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol Biol Cell 16:2285–2300. https://doi.org/10.1091/mbc.e04-11-0987
  • Banerjee D, Bloom AL, Panepinto JC (2016) Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans. Mol Microbiol 102:306–320. https://doi.org/10.1111/mmi.13461
  • Beyer R, Jandric Z, Zutz C, Gregori C, Willinger B, Jacobsen ID, Kovarik P, Strauss J, Schüller C (2018) Competition of Candida glabrata against Lactobacillus is Hog1 dependent. Cell Microbiol 20:e12943. https://doi.org/10.1111/cmi.12943
  • Calera JA, Zhao XJ, Calderone R (2000) Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans. Infect Immun 68:518–525
  • Chauhan N, Inglis D, Román E, Pla J, Li D, Calera JA, Calderone R (2003) Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress. Eukaryot Cell 2:1018–1024
  • Cheetham J, MacCallum DM, Doris KS, da Silva Dantas A, Scorfield S, Odds F, Smith DA, Quinn J (2011) MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans. J Biol Chem 286:42002–42016. https://doi.org/10.1074/jbc.M111.265231
  • Cheetham J, Smith DA, da Silva DA, Doris KS, Patterson MJ, Bruce CR, Quinn J (2007) A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans. Mol Biol Cell 18:4603–4614
  • Cole GT, Seshan KR, Phaneuf M, Lynn KT (1991) Chlamydospore-like cells of Candida albicans in the gastrointestinal tract of infected, immunocompromised mice. Can J Microbiol 37:637–646
  • Correia I, Alonso-Monge R, Pla J (2016) The Hog1 MAP kinase promotes the recovery from cell cycle arrest induced by hydrogen peroxide in Candida albicans. Front Microbiol 7:2133. https://doi.org/10.3389/fmicb.2016.02133
  • 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: 982–985
  • Cullen PJ et al (2004) A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev 18:1695–1708. https://doi.org/10.1101/gad.1178604
  • de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3: 735–740
  • Eisman B, Alonso-Monge R, Román E, Arana DM, Nombela C, Pla J (2006) The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans. Eukaryot Cell 5:347–358
  • 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
  • Enjalbert B, Smith DA, Cornell MJ, Alam I, Nicholls S, Brown AJ, Quinn J (2006) Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans. Mol Biol Cell 17:1018–1032
  • Furukawa K, Hoshi Y, Maeda T, Nakajima T, Abe K (2005) Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress. Mol Microbiol 56:1246–1261
  • Gow NA, van de Veerdonk FL, Brown AJ, Netea MG (2012) Candida albicans morphogenesis and host defence: discriminating invasion from colonization. Nat Rev Microbiol 10:112–122. https://doi.org/10.1038/nrmicro2711
  • 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
  • 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: 21–32
  • 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
  • Herskowitz (1995) MAP kinase pathways in yeast: for mating and more. Cell 80: 187–197
  • Hohmann S (2015) An integrated view on a eukaryotic osmoregulation system. Curr Genet 61:373–382. https://doi.org/10.1007/s00294-015-0475-0
  • Homman S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiolo Mol Biol Rev 66: 300–372
  • Huang G, Wang H, Chou S, Nie X, Chen J, Liu H (2006) Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci U S A 103:12813–12818
  • 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
  • Ikner A, Shiozaki K (2005) Yeast signaling pathways in the oxidative stress response. Mutat Res 569:13–27
  • Iliev ID, Leonardi I (2017) Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat Rev Immunol 17:635–646. https://doi.org/10.1038/nri.2017.55
  • Kultz D (1998) Phylogenetic and functional classification of mitogen- and stress-activated protein kinases. J MolEvol 46:571–588
  • Leonardi I, Li X, Semon A, Li D, Doron I, Putzel G, Bar A, Prieto D, Rescigno M, McGovern DPB, Pla J, Iliev ID (2018) CX3CR1(+) mononuclear phagocytes control immunity to intestinal fungi. Science 359:232–236. https://doi.org/10.1126/science.aao1503
  • Liang SH, Cheng JH, Deng FS, Tsai PA, Lin CH (2014) A novel function for Hog1 stress-activated protein kinase in controlling white-opaque switching and mating in Candida albicans. Eukaryot Cell 13:1557–1566. https://doi.org/10.1128/ec.00235-14
  • Liu H (2001) Transcriptional control of dimorphism in Candida albicans. Curr Opin Microbiol 4:728–735
  • Ma D, Li R (2013) Current understanding of HOG-MAPK pathway in Aspergillus fumigatus. Mycopathologia 175:13–23. https://doi.org/10.1007/s11046-012-9600-5
  • Monge RA, Roman E, Nombela C, Pla J (2006) The MAP kinase signal transduction network in Candida albicans. Microbiology 152:905–912. https://doi.org/10.1099/mic.0.28616-0
  • Morales-Menchen A et al (2018) Non-canonical activities of Hog1 control sensitivity of Candida albicans to killer toxins from Debaryomyces hansenii. Front Cell Infect Microbiol 8:135. https://doi.org/10.3389/fcimb.2018.00135
  • 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: 1399–1413
  • Moye-Rowley WS, Harshman KD, Parker CS (1989) Yeast YAP1 encodes a novel form of the Jun family of transcriptional activator proteins. Genes Dev 3:283–292
  • Murad AM et al (2001) NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J 20:4742–4752
  • Navarro-García F, Eisman B, Fiuza SM, Nombela C, Pla J (2005) The MAP kinase Mkc1p is activated under different stress conditions in Candida albicans. Microbiology 151:2737–2749
  • Netea MG, Brown GD (2012) Fungal infections: the next challenge. Curr Opin Microbiol 15:403–405. https://doi.org/10.1016/j.mib.2012.07.002
  • O’Rourke SM, Herskowitz I (2002) A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein and functions in parallel with the Sho1 branch. Mol Cell Biol 22:4739–4749
  • Pande K, Chen C, Noble SM (2013) Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism. Nat Genet 45:1088–1091
  • Perez P, Cansado J (2010) Cell integrity signaling and response to stress in fission yeast. Curr Protein Pept Sci 11:680–692
  • Posas F, Saito H (1997) Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science 276:1702–1705
  • Posas F, Wurgler-Murphy SM, Maeda T, Witten EA, Thai TC, Saito H (1996) Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell 86:865–875
  • 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: 17249–17255
  • Prieto AD, Román E, Correia I, Pla J (2014) The HOG pathway is critical for the colonization of the mouse gastrointestinal tract by Candida albicans. PLoS One 9:e87128
  • Proft M, Pascual-Ahuir A, de Nadal E, Arino J, Serrano R, Posas F (2001) Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress. EMBO J 20:1123–1133
  • 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 40:1067–1083
  • Rodriguez-Gabriel MA, Russell P (2005) Distinct signaling pathways respond to arsenite and reactive oxygen species in Schizosaccharomyces pombe. Eukaryot Cell 4:1396–1402
  • Román E, Arana DM, Nombela C, Alonso-Monge R, Pla J (2007) MAP kinase pathways as regulators of fungal virulence. Trends Microbiol 15:181–190
  • Román E, Cottier F, Ernst JF, Pla J (2009) Msb2 signaling mucin controls activation of Cek1 mitogen-activated protein kinase in Candida albicans. Eukaryot Cell 8:1235–1249
  • Román E, Nombela C, Pla J (2005) The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans. Mol Cell Biol 25:10611–10627
  • Romani L (2011) Immunity to fungal infections. Nat Rev Immunol 11:275–288. https://doi.org/10.1038/nri2939
  • Rooney PJ, Klein BS (2002) Linking fungal morphogenesis with virulence. Cell Microbiol 4:127–137
  • Saito H (2010) Regulation of cross-talk in yeast MAPK signaling pathways. Curr Opin Microbiol 13:677–683
  • San José C, Alonso-Monge R, Pérez-Díaz RM, Pla J, Nombela C (1996) The mitogen-activated protein kinase homolog HOG1 gene controls glycerol accumulation in the pathogenic fungus Candida albicans. J Bacteriol 178:5850–5852
  • Singh KK (2000) The Saccharomyces cerevisiae Sln1p-Ssk1p two-component system mediates response to oxidative stress and in an oxidant-specific fashion. Free RadicBiol Med 29:1043–1050
  • Sonneborn A, Bockmuhl DP, Ernst JF (1999) Chlamydospore formation in Candida albicans requires the Efg1p morphogenetic regulator. Infect Immun 67:5514–5517
  • Srikantha T, Borneman AR, Daniels KJ, Pujol C, Wu W, Seringhaus MR, Gerstein M, Yi S, Snyder M, Soll DR (2006) TOS9 regulates white-opaque switching in Candida albicans. Eukaryot Cell 5:1674–1687
  • Staib P, Morschhauser J (2005) Differential expression of the NRG1 repressor controls species-specific regulation of chlamydospore development in Candida albicans and Candida dubliniensis. Mol Microbiol 55:637–652
  • Staib P, Morschhauser J (2007) Chlamydospore formation in Candida albicans and Candida dubliniensis --an enigmatic developmental programme. Mycoses 50:1–12
  • Su C, Lu Y, Liu H (2013) Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity. Mol Biol Cell 24:385–397. https://doi.org/10.1091/mbc.E12-06-0477
  • Urrialde V, Alburquerque B, Guirao-Abad JP, Pla J, Argüelles JC, Alonso-Monge R (2017) Arsenic inorganic compounds cause oxidative stress mediated by the transcription factor PHO4 in Candida albicans. Microbiol Res 203:10–18. https://doi.org/10.1016/j.micres.2017.06.004
  • Urrialde V, Prieto D, Pla J, Alonso-Monge R (2015) The Pho4 transcription factor mediates the response to arsenate and arsenite in Candida albicans. Front Microbiol 6:118. https://doi.org/10.3389/fmicb.2015.00118
  • Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180
  • Zhang X, De Micheli M, Coleman ST, Sanglard D, Moye-Rowley WS (2000) Analysis of the oxidative stress regulation of the Candida albicans transcription factor. Cap1p Mol Microbiol 36:618–629