Skip to main content

Advertisement

SpringerLink
Log in

Current Understanding of HOG-MAPK Pathway in Aspergillus fumigatus

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

Aspergillus fumigatus is an important opportunistic fungal pathogen that causes lethal systemic invasive aspergillosis. It must be able to adapt to stress in the microenvironment during host invasion and systemic spread. The high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) signaling pathway is a key element that controls adaptation to environmental stress. It plays a critical role in the virulence of several fungal pathogens. In this review, we summarize the current knowledge about the functions of different components of the HOG-MAPK pathway in A. fumigatus through mutant analysis or inferences from the genome annotation, focusing on their roles in adaptation to stress, regulation of infection-related morphogenesis, and effect on virulence. We also briefly compare the functions of the HOG pathway in A. fumigatus with those in the model fungi Saccharomyces cerevisiae and Aspergillus nidulans as well as several other human and plant pathogens including Candida albicans, Cryptococcus neoformans, and Magnaporthe oryzae. The genes described in this review mainly include tcsB, fos1, skn7, sho1, pbs2, and sakA whose deletion mutants have already been established in A. fumigatus. Among them, fos1 has been considered a virulence factor in A. fumigatus, indicating that components of the HOG pathway may be suitable as targets for developing new fungicides. However, quite a few of the genes of this pathway, such as sskA (ssk1), sskB, steC, and downstream regulator genes, are not well characterized. System biology approaches may contribute to a more comprehensive understanding of HOG pathway functions with dynamic details.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 1999;12:310–50.

    PubMed  CAS  Google Scholar 

  2. Balloy V, Chignard M. The innate immune response to Aspergillus fumigatus. Microbes Infect. 2009;11:919–27.

    Article  PubMed  CAS  Google Scholar 

  3. Brakhage AA, Langfelder K. Menacing mold: the molecular biology of Aspergillus fumigatus. Annu Rev Microbiol. 2002;56:433–55.

    Article  PubMed  CAS  Google Scholar 

  4. Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs. 2007;67:1567–601.

    Article  PubMed  CAS  Google Scholar 

  5. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005;18:44–69.

    Article  PubMed  CAS  Google Scholar 

  6. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26:781–3; quiz 804–5.

  7. Fortun J, Martin-Davila P, Moreno S, et al. Risk factors for invasive aspergillosis in liver transplant recipients. Liver Transpl. 2002;8:1065–70.

    Article  PubMed  Google Scholar 

  8. Abad A, Fernández-Molina JV, Bikandi J, et al. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol. 2010;27:155–82.

    Article  PubMed  Google Scholar 

  9. Hartmann T, Sasse C, Schedler A, et al. Shaping the fungal adaptome–stress responses of Aspergillus fumigatus. Int J Med Microbiol. 2011;301:408–16.

    Article  PubMed  CAS  Google Scholar 

  10. Zarember KA, Sugui JA, Chang YC, et al. Human polymorphonuclear leukocytes inhibit Aspergillus fumigatus conidial growth by lactoferrin-mediated iron depletion. J Immunol. 2007;178:6367–73.

    PubMed  CAS  Google Scholar 

  11. Franzon VL, Arondel J, Sansonetti PJ. Contribution of superoxide dismutase and catalase activities to Shigella flexneri pathogenesis. Infect Immun. 1990;58:529–35.

    PubMed  CAS  Google Scholar 

  12. Gustin MC, Albertyn J, Alexander M, et al. MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1998;62:1264–300.

    PubMed  CAS  Google Scholar 

  13. Cobb MH, Goldsmith EJ. How MAP kinases are regulated. J Biol Chem. 1995;270:14843–6.

    Article  PubMed  CAS  Google Scholar 

  14. Marshall CJ. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet. 1994;4:82–9.

    Article  CAS  Google Scholar 

  15. Morillon A, Springer M, Lesage P. Activation of the Kss1 invasive-filamentous growth pathway induces Ty1 transcription and retrotransposition in Saccharomyces cerevisiae. Mol Cell Biol. 2000;20:5766–76.

    Article  PubMed  CAS  Google Scholar 

  16. Rep M, Reiser V, Gartner U, et al. Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p. Mol Cell Biol. 1999;19:5474–85.

    PubMed  CAS  Google Scholar 

  17. Proft M, Serrano R. Repressors and upstream repressing sequences of the stress-regulated ENA1 gene in Saccharomyces cerevisiae: bZIP protein Sko1p confers HOG-dependent osmotic regulation. Mol Cell Biol. 1999;19:537–46.

    PubMed  CAS  Google Scholar 

  18. Posas F, Saito H. Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK. Science. 1997;276:1702–5.

    Article  PubMed  CAS  Google Scholar 

  19. Hohmann S. Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae. FEBS Lett. 2009;583:4025–9.

    Article  PubMed  CAS  Google Scholar 

  20. Maeda T, Takekawa M, Saito H. Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science. 1995;269:554–8.

    Article  PubMed  CAS  Google Scholar 

  21. Blomberg A, Adler L. Physiology of osmotolerance in fungi. Adv Microb Physiol. 1992;33:145–212.

    Article  PubMed  CAS  Google Scholar 

  22. Rep M, Krantz M, Thevelein JM, Hohmann S. The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes. J Biol Chem. 2000;275:8290–300.

    Article  PubMed  CAS  Google Scholar 

  23. Yaakov G, Duch A, García-Rubio M, et al. The stress-activated protein kinase Hog1 mediates S phase delay in response to osmostress. Mol Biol Cell. 2009;20:3572–82.

    Article  PubMed  CAS  Google Scholar 

  24. Lawrence CL, Botting CH, Antrobus R, Coote PJ. Evidence of a new role for the high-osmolarity glycerol mitogen-activated protein kinase pathway in yeast: regulating adaptation to citric acid stress. Mol Cell Biol. 2004;24:3307–23.

    Article  PubMed  CAS  Google Scholar 

  25. Bilsland E, Molin C, Swaminathan S, Ramne A, Sunnerhagen P. Rck1 and Rck2 MAPKAP kinases and the HOG pathway are required for oxidative stress resistance. Mol Microbiol. 2004;53:1743–56.

    Article  PubMed  CAS  Google Scholar 

  26. Sotelo J, Rodríguez-Gabriel MA. Mitogen-activated protein kinase Hog1 is essential for the response to arsenite in Saccharomyces cerevisiae. Eukaryot Cell. 2006;5:1826–30.

    Article  PubMed  CAS  Google Scholar 

  27. Degols G, Russell P. Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe. Mol Cell Biol. 1997;17:3356–63.

    PubMed  CAS  Google Scholar 

  28. Winkler A, Arkind C, Mattison CP, et al. Heat stress activates the yeast high-osmolarity glycerol mitogen-activated protein kinase pathway, and protein tyrosine phosphatases are essential under heat stress. Eukaryot Cell. 2002;1:163–73.

    Article  PubMed  CAS  Google Scholar 

  29. Alonso-Monge R, Navarro-García F, Molero G, et al. Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J Bacteriol. 1999;181:3058–68.

    PubMed  CAS  Google Scholar 

  30. Bahn YS, Kojima K, Cox GM, Heitman J. Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol Biol Cell. 2005;16:2285–300.

    Article  PubMed  CAS  Google Scholar 

  31. Zhang Y, Zhao J, Fang W, et al. Mitogen-activated protein kinase hog1 in the entomopathogenic fungus Beauveria bassiana regulates environmental stress responses and virulence to insects. Appl Environ Microbiol. 2009;75:3787–95.

    Article  PubMed  CAS  Google Scholar 

  32. Igbaria A, Lev S, Rose MS, et al. Distinct and combined roles of the MAP kinases of Cochliobolus heterostrophus in virulence and stress responses. Mol Plant Microbe Interact. 2008;21:769–80.

    Article  PubMed  CAS  Google Scholar 

  33. Jung KW, Strain AK, Nielsen K, et al. Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway. Fungal Genet Biol. 2012;49:332–45.

    Article  PubMed  CAS  Google Scholar 

  34. Nierman WC, Pain A, Anderson MJ, et al. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005;438:1151–6.

    Article  PubMed  CAS  Google Scholar 

  35. da Silva Ferreira ME, Kress MR, Savoldi M, et al. The akuB(KU80) mutant deficient for nonhomologous end joining is a powerful tool for analyzing pathogenicity in Aspergillus fumigatus. Eukaryot Cell. 2006;5:207–11.

    Article  PubMed  CAS  Google Scholar 

  36. Krappmann S, Sasse C, Braus GH. Gene targeting in Aspergillus fumigatus by homologous recombination is facilitated in a nonhomologous end- joining-deficient genetic background. Eukaryot Cell. 2006;5:212–5.

    Article  PubMed  CAS  Google Scholar 

  37. Weidner G, d’Enfert C, Koch A, et al. Development of a homologous transformation system for the human pathogenic fungus Aspergillus fumigatus based on the pyrG gene encoding orotidine 5’-monophosphate decarboxylase. Curr Genet. 1998;33:378–85.

    Article  PubMed  CAS  Google Scholar 

  38. Song L, Sudhakar P, Wang W, et al. A genome-wide study of two-component signal transduction systems in eight newly sequenced mutans streptococci strains. BMC Genomics. 2012;13:128.

    Article  PubMed  CAS  Google Scholar 

  39. Gotoh Y, Eguchi Y, Watanabe T, et al. Two-component signal transduction as potential drug targets in pathogenic bacteria. Curr Opin Microbiol. 2010;13:232–9.

    Article  PubMed  CAS  Google Scholar 

  40. Ketela T, Brown JL, Stewart RC, Bussey H. Yeast Skn7p activity is modulated by the Sln1p-Ypd1p osmosensor and contributes to regulation of the HOG pathway. Mol Gen Genet. 1998;259:372–8.

    Article  PubMed  CAS  Google Scholar 

  41. Li S, Ault A, Malone CL, et al. The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. EMBO J. 1998;17:6952–62.

    Article  PubMed  CAS  Google Scholar 

  42. Alex LA, Korch C, Selitrennikoff CP, Simon MI. COS1, a two-component histidine kinase that is involved in hyphal development in the opportunistic pathogen Candida albicans. Proc Natl Acad Sci USA. 1998;95:7069–73.

    Article  PubMed  CAS  Google Scholar 

  43. Brewster JL, de Valoir T, Dwyer ND, et al. An osmosensing signal transduction pathway in yeast. Science. 1993;259:1760–2.

    Article  PubMed  CAS  Google Scholar 

  44. Posas F, Wurgler-Murphy SM, Maeda T, et al. Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 “two-component” osmosensor. Cell. 1996;86:865–75.

    Article  PubMed  CAS  Google Scholar 

  45. Virginia M, Appleyard CL, McPheat WL, Stark MJ. A novel ‘two-component’ protein containing histidine kinase and response regulator domains required for sporulation in Aspergillus nidulans. Curr Genet. 2000;37:364–72.

    Article  PubMed  CAS  Google Scholar 

  46. Kruppa M, Calderone R. Two-component signal transduction in human fungal pathogens. FEMS Yeast Res. 2006;6:149–59.

    Article  PubMed  CAS  Google Scholar 

  47. Bahn YS, Kojima K, Cox GM, Heitman J. A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans. Mol Biol Cell. 2006;17:3122–35.

    Article  PubMed  CAS  Google Scholar 

  48. Oide S, Liu J, Yun SH, et al. Histidine kinase two-component response regulator proteins regulate reproductive development, virulence, and stress responses of the fungal cereal pathogens Cochliobolus heterostrophus and Gibberella zeae. Eukaryot Cell. 2010;9:1867–80.

    Article  PubMed  CAS  Google Scholar 

  49. Tao W, Deschenes RJ, Fassler JS. Intracellular glycerol levels modulate the activity of Sln1p, a Saccharomyces cerevisiae two-component regulator. J Biol Chem. 1999;274:360–7.

    Article  PubMed  CAS  Google Scholar 

  50. Calera JA, Choi GH, Calderone RA. Identification of a putative histidine kinase two-component phosphorelay gene (CaHK1) in Candida albicans. Yeast. 1998;14:665–74.

    Article  PubMed  CAS  Google Scholar 

  51. Nagahashi S, Mio T, Ono N, et al. Isolation of CaSLN1 and CaNIK1, the genes for osmosensing histidine kinase homologues, from the pathogenic fungus Candida albicans. Microbiology. 1998;144:425–32.

    Article  PubMed  CAS  Google Scholar 

  52. Srikantha T, Tsai L, Daniels K, et al. The two-component hybrid kinase regulator CaNIK1 of Candida albicans. Microbiology. 1998;144:2715–29.

    Article  PubMed  CAS  Google Scholar 

  53. Yamada-Okabe T, Mio T, Ono N, et al. Roles of three histidine kinase genes in hyphal development and virulence of the pathogenic fungus Candida albicans. J Bacteriol. 1999;181:7243–7.

    PubMed  CAS  Google Scholar 

  54. Buck V, Quinn J, Soto Pino T, et al. Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway. Mol Biol Cell. 2001;12:407–19.

    PubMed  CAS  Google Scholar 

  55. Catlett NL, Yoder OC, Turgeon BG. Whole-genome analysis of two-component signal transduction genes in fungal pathogens. Eukaryot Cell. 2003;2:1151–61.

    Article  PubMed  CAS  Google Scholar 

  56. Motoyama T, Ochiai N, Morita M, et al. Involvement of putative response regulator genes of the rice blast fungus Magnaporthe oryzae in osmotic stress response, fungicide action, and pathogenicity. Curr Genet. 2008;54:185–95.

    Article  PubMed  CAS  Google Scholar 

  57. Hagiwara D, Mizuno T, Abe K. Characterization of NikA histidine kinase and two response regulators with special reference to osmotic adaptation and asexual development in Aspergillus nidulans. Biosci Biotechnol Biochem. 2009;73:1566–71.

    Article  PubMed  CAS  Google Scholar 

  58. Calera JA, Zhao XJ, De Bernardis F, Sheridan M, Calderone R. Avirulence of Candida albicans CaHK1 mutants in a murine model of hematogenously disseminated candidiasis. Infect Immun. 1999;67:4280–4.

    PubMed  CAS  Google Scholar 

  59. Chauhan N, Latge JP, Calderone R. Signalling and oxidant adaptation in Candida albicans and Aspergillus fumigatus. Nat Rev Microbiol. 2006;4:435–44.

    Article  PubMed  CAS  Google Scholar 

  60. Pott GB, Miller TK, Bartlett JA, et al. The isolation of FOS-1, a gene encoding a putative two-component histidine kinase from Aspergillus fumigatus. Fungal Genet Biol. 2000;31:55–67.

    Article  PubMed  CAS  Google Scholar 

  61. Hagiwara D, Matsubayashi Y, Marui J, et al. Characterization of the NikA histidine kinase implicated in the phosphorelay signal transduction of Aspergillus nidulans, with special reference to fungicide responses. Biosci Biotechnol Biochem. 2007;71:844–7.

    Article  PubMed  CAS  Google Scholar 

  62. Motoyama T, Kadokura K, Ohira T, et al. A two-component histidine kinase of the rice blast fungus is involved in osmotic stress response and fungicide action. Fungal Genet Biol. 2005;42:200–12.

    Article  PubMed  CAS  Google Scholar 

  63. Selitrennikoff CP, Stevens DA. fos-1, a putative histidine kinase as a virulence factor for systemic aspergillosis. Med Mycol. 2002;40:259–62.

    PubMed  Google Scholar 

  64. Ota IM, Varshavsky A. A yeast protein similar to bacterial two-component regulators. Science. 1993;262:566–9.

    Article  PubMed  CAS  Google Scholar 

  65. Zhang H, Liu K, Zhang X, et al. A two-component histidine kinase, MoSLN1, is required for cell wall integrity and pathogenicity of the rice blast fungus, Magnaporthe oryzae. Curr Genet. 2010;56:517–28.

    Article  PubMed  CAS  Google Scholar 

  66. Furukawa K, Katsuno Y, Urao T, et al. Isolation and functional analysis of a gene, tcsB, encoding a transmembrane hybrid-type histidine kinase from Aspergillus nidulans. Appl Environ Microbiol. 2002;68:5304–10.

    Article  PubMed  CAS  Google Scholar 

  67. Du C, Sarfati J, Latge JP, Calderone R. The role of the sakA (Hog1) and tcsB (sln1) genes in the oxidant adaptation of Aspergillus fumigatus. Med Mycol. 2006;44:211–8.

    Article  PubMed  CAS  Google Scholar 

  68. Du C, Li R, Ma S, Wang D. Cloning of Aspergillus fumigatus histidine kinase gene fragment and its expression during invasive infection. Mycopathologia. 2002;153:5–10.

    Article  PubMed  CAS  Google Scholar 

  69. Brown JL, Bussey H, Stewart RC. Yeast Skn7p functions in a eukaryotic two-component regulatory pathway. EMBO J. 1994;13:5186–94.

    PubMed  CAS  Google Scholar 

  70. Morgan BA, Banks GR, Toone WM, et al. The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J. 1997;16:1035–44.

    Article  PubMed  CAS  Google Scholar 

  71. Krems B, Charizanis C, Entian KD. The response regulator-like protein Pos9/Skn7 of Saccharomyces cerevisiae is involved in oxidative stress resistance. Curr Genet. 1996;29:327–34.

    Article  PubMed  CAS  Google Scholar 

  72. He XJ, Mulford KE, Fassler JS. Oxidative stress function of the Saccharomyces cerevisiae Skn7 receiver domain. Eukaryot Cell. 2009;8:768–78.

    Google Scholar 

  73. Raitt DC, Johnson AL, Erkine AM, et al. The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress. Mol Biol Cell. 2000;11:2335–47.

    PubMed  CAS  Google Scholar 

  74. Lu JM, Deschenes RJ, Fassler JS. Saccharomyces cerevisiae histidine phosphotransferase Ypd1p shuttles between the nucleus and cytoplasm for SLN1-dependent phosphorylation of Ssk1p and Skn7p. Eukaryot Cell. 2003;2:1304–14.

    Article  PubMed  CAS  Google Scholar 

  75. Brown JL, North S, Bussey H. SKN7, a yeast multicopy suppressor of a mutation affecting cell wall beta-glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors. J Bacteriol. 1993;175:6908–15.

    PubMed  CAS  Google Scholar 

  76. Ruprich-Robert G, Chapeland-Leclerc F, Boisnard S, et al. Contributions of the response regulators Ssk1p and Skn7p in the pseudohyphal development, stress adaptation, and drug sensitivity of the opportunistic yeast Candida lusitaniae. Eukaryot Cell. 2008;7:1071–4.

    Article  PubMed  CAS  Google Scholar 

  77. Singh P, Chauhan N, Ghosh A, et al. SKN7 of Candida albicans: mutant construction and phenotype analysis. Infect Immun. 2004;72:2390–4.

    Article  PubMed  CAS  Google Scholar 

  78. Coenjaerts FE, Hoepelman AI, Scharringa J, et al. The Skn7 response regulator of Cryptococcus neoformans is involved in oxidative stress signalling and augments intracellular survival in endothelium. FEMS Yeast Res. 2006;6:652–61.

    Article  PubMed  CAS  Google Scholar 

  79. Vargas-Pérez I, Sánchez O, Kawasaki L, Georgellis D, Aguirre J. Response regulators SrrA and SskA are central components of a phosphorelay system involved in stress signal transduction and asexual sporulation in Aspergillus nidulans. Eukaryot Cell. 2007;6:1570–83.

    Article  PubMed  CAS  Google Scholar 

  80. Lamarre C, Ibrahim-Granet O, Du C, et al. Characterization of the SKN7 ortholog of Aspergillus fumigatus. Fungal Genet Biol. 2007;44:682–90.

    Article  PubMed  CAS  Google Scholar 

  81. Wormley FL Jr, Heinrich G, Miller JL, Perfect JR, Cox GM. Identification and characterization of an SKN7 homologue in Cryptococcus neoformans. Infect Immun. 2005;73:5022–30.

    Article  PubMed  CAS  Google Scholar 

  82. Maeda T, Wurgler-Murphy SM, Saito H. A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature. 1994;369:242–5.

    Article  PubMed  CAS  Google Scholar 

  83. Menon V, Li D, Chauhan N, et al. Functional studies of the Ssk1p response regulator protein of Candida albicans as determined by phenotypic analysis of receiver domain point mutants. Mol Microbiol. 2006;62:997–1013.

    Article  PubMed  CAS  Google Scholar 

  84. Chauhan N, Inglis D, Roman E, et al. 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. 2003;2:1018–24.

    Article  PubMed  CAS  Google Scholar 

  85. Du C, Calderone R, Richert J, et al. Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. Infect Immun. 2005;73:865–71.

    Article  PubMed  CAS  Google Scholar 

  86. Calera JA, Zhao XJ, Calderone R. Defective hyphal development and avirulence caused by a deletion of the CSSK1 response regulator gene in Candida albicans. Infect Immun. 2000;68:518–25.

    Article  PubMed  CAS  Google Scholar 

  87. Singh KK. The Saccharomyces cerevisiae Sln1p-Ssk1p two-component system mediates response to oxidative stress and in an oxidant-specific fashion. Free Radic Biol Med. 2000;29:1043–50.

    Article  PubMed  CAS  Google Scholar 

  88. Roman E, Nombela C, Pla J. The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans. Mol Cell Biol. 2005;25:10611–27.

    Article  PubMed  CAS  Google Scholar 

  89. Boisnard S, Ruprich-Robert G, Florent M, et al. Role of Sho1p adaptor in the pseudohyphal development, drugs sensitivity, osmotolerance and oxidant stress adaptation in the opportunistic yeast Candida lusitaniae. Yeast. 2008;25:849–59.

    Article  PubMed  CAS  Google Scholar 

  90. O’Rourke SM, Herskowitz I. The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev. 1998;12:2874–86.

    Article  PubMed  Google Scholar 

  91. Liu W, Zhou X, Li G, et al. Multiple plant surface signals are sensed by different mechanisms in the rice blast fungus for appressorium formation. PLoS Pathog. 2011;7:e1001261.

    Article  PubMed  CAS  Google Scholar 

  92. Lanver D, Mendoza-Mendoza A, Brachmann A, Kahmann R. Sho1 and Msb2-related proteins regulate appressorium development in the smut fungus Ustilago maydis. Plant Cell. 2010;22:2085–101.

    Article  PubMed  CAS  Google Scholar 

  93. Ma Y, Qiao J, Liu W, et al. The Sho1 sensor regulates growth, morphology, and oxidant adaptation in Aspergillus fumigatus but is not essential for development of invasive pulmonary aspergillosis. Infect Immun. 2008;76:1695–701.

    Article  PubMed  CAS  Google Scholar 

  94. Yang F, Ma D, Wan Z, et al. The Role of sho1 in Polarized Growth of Aspergillus fumigatus. Mycopathologia. 2011;172:347–55.

    Article  PubMed  Google Scholar 

  95. Boguslawski G, Polazzi JO. Complete nucleotide sequence of a gene conferring polymyxin B resistance on yeast: similarity of the predicted polypeptide to protein kinases. Proc Natl Acad Sci USA. 1987;84:5848–52.

    Article  PubMed  CAS  Google Scholar 

  96. Furukawa K, Hoshi Y, Maeda T, et al. Aspergillus nidulans HOG pathway is activated only by two-component signalling pathway in response to osmotic stress. Mol Microbiol. 2005;56:1246–61.

    Article  PubMed  CAS  Google Scholar 

  97. Cheetham J, Smith DA. da Silva Dantas A, et al. A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans. Mol Biol Cell. 2007;18:4603–14.

    Article  PubMed  CAS  Google Scholar 

  98. Arana DM, Nombela C, Alonso-Monge R, Pla J. The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans. Microbiology. 2005;151:1033–49.

    Article  PubMed  CAS  Google Scholar 

  99. Cheetham J, MacCallum DM, Doris KS, et al. MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans. J Biol Chem. 2011;286:42002–16.

    Article  PubMed  CAS  Google Scholar 

  100. Lara-Rojas F, Sánchez O, Kawasaki L, Aguirre J. Aspergillus nidulans transcription factor AtfA interacts with the MAPK SakA to regulate general stress responses, development and spore functions. Mol Microbiol. 2011;80:436–54.

    Article  PubMed  CAS  Google Scholar 

  101. Argimón S, Fanning S, Blankenship JR, Mitchell AP. Interaction between the Candida albicans high-osmolarity glycerol (HOG) pathway and the response to human beta-defensins 2 and 3. Eukaryot Cell. 2011;10:272–5.

    Article  PubMed  CAS  Google Scholar 

  102. Reyes G, Romans A, Nguyen CK, May GS. Novel mitogen-activated protein kinase MpkC of Aspergillus fumigatus is required for utilization of polyalcohol sugars. Eukaryot Cell. 2006;5:1934–40.

    Article  PubMed  CAS  Google Scholar 

  103. Kawasaki L, Sánchez O, Shiozaki K, Aguirre J. SakA MAP kinase is involved in stress signal transduction, sexual development and spore viability in Aspergillus nidulans. Mol Microbiol. 2002;45:1153–63.

    Article  PubMed  CAS  Google Scholar 

  104. Wong Sak Hoi J, Lamarre C, Beau R, et al. A novel family of dehydrin-like proteins is involved in stress response in the human fungal pathogen Aspergillus fumigatus. Mol Biol Cell. 2011;22:1896–906.

    Article  PubMed  CAS  Google Scholar 

  105. Arana DM, Alonso-Monge R, Du C, et al. Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans. Cell Microbiol. 2007;9:1647–59.

    Article  PubMed  CAS  Google Scholar 

  106. Alonso-Monge R, Carvaihlo S, Nombela C, Rial E, Pla J. The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans. Microbiology. 2009;155:413–23.

    Article  PubMed  CAS  Google Scholar 

  107. Moriwaki A, Kubo E, Arase S, Kihara J. Disruption of SRM1, a mitogen-activated protein kinase gene, affects sensitivity to osmotic and ultraviolet stressors in the phytopathogenic fungus Bipolaris oryzae. FEMS Microbiol Lett. 2006;257:253–61.

    Article  PubMed  CAS  Google Scholar 

  108. Noguchi R, Banno S, Ichikawa R, et al. Identification of OS-2 MAP kinasedependent genes induced in response to osmotic stress, antifungal agent fludioxonil, and heat shock in Neurospora crassa. Fungal Genet Biol. 2007;44:208–18.

    Google Scholar 

  109. Kim JH, Chan KL, Faria NC, et al. Targeting the oxidative stress response system of fungi with redox-potent chemosensitizing agents. Front Microbiol. 2012;3:88.

    PubMed  Google Scholar 

  110. Kojima K, Takano Y, Yoshimi A, Tanaka C, Kikuchi T, Okuno T. Fungicide activity through activation of a fungal signalling pathway. Mol Microbiol. 2004;53:1785–96.

    Article  PubMed  CAS  Google Scholar 

  111. Wong Sak Hoi J, Beau R, Latgé JP. A novel dehydrin-like protein from Aspergillus fumigatus regulates freezing tolerance. Fungal Genet Biol. 2012;49:210–6.

    Article  PubMed  CAS  Google Scholar 

  112. Xue T, Nguyen CK, Romans A, May GS. A mitogen-activated protein kinase that senses nitrogen regulates conidial germination and growth in Aspergillus fumigatus. Eukaryot Cell. 2004;3:557–60.

    Article  PubMed  CAS  Google Scholar 

  113. Mehrabi R, Zwiers LH, de Waard MA, Kema GH. MgHog1 regulates dimorphism and pathogenicity in the fungal wheat pathogen Mycosphaerella graminicola. Mol Plant Microbe Interact. 2006;19:1262–9.

    Article  PubMed  CAS  Google Scholar 

  114. Park SM, Choi ES, Kim MJ, Cha BJ, Yang MS, Kim DH. Characterization of HOG1 homologue, CpMK1, from Cryphonectria parasitica and evidence for hypovirus-mediated perturbation of its phosphorylation in response to hypertonic stress. Mol Microbiol. 2004;51:1267–77.

    Article  PubMed  CAS  Google Scholar 

  115. Segmüller N, Ellendorf U, Tudzynski B, Tudzynski P. BcSAK1, a stress-activated mitogen-activated protein kinase, is involved in vegetative differentiation and pathogenicity in Botrytis cinerea. Eukaryot Cell. 2007;6:211–21.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was sponsored by the National Foundation of Natural Sciences in China (No. 30930006).

Author information

Authors and Affiliations

  1. Department of Dermatology, Peking University First Hospital, and Research Center for Medical Mycology, Peking University, No. 8 Xi-Shi-Ku St. Xicheng District, Beijing, 100034, China

    Dongmei Ma & Ruoyu Li

Authors
  1. Dongmei Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruoyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruoyu Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, D., Li, R. Current Understanding of HOG-MAPK Pathway in Aspergillus fumigatus . Mycopathologia 175, 13–23 (2013). https://doi.org/10.1007/s11046-012-9600-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-012-9600-5

Keywords

Search

Navigation