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The Alkaline Response Pathway: Identification of a Novel Rim Pathway Activator
Microorganisms that cause human disease use various cues to determine when they encounter a host. One of these signals is the slightly alkaline pH of human tissues. We have defined components of a pH-responsive signaling pathway in the human fungal pathogen Cryptococcus neoformans. This particular signaling pathway is specific for fungi and important for the virulence of several plant and animal pathogens. We have identified a previously unknown protein that activates this pH-sensing pathway. This protein and its downstream signaling pathway play a major role in the interaction of this fungal pathogen and the host immune system.
Vyšlo v časopise: The Alkaline Response Pathway: Identification of a Novel Rim Pathway Activator. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005159
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005159Souhrn
Microorganisms that cause human disease use various cues to determine when they encounter a host. One of these signals is the slightly alkaline pH of human tissues. We have defined components of a pH-responsive signaling pathway in the human fungal pathogen Cryptococcus neoformans. This particular signaling pathway is specific for fungi and important for the virulence of several plant and animal pathogens. We have identified a previously unknown protein that activates this pH-sensing pathway. This protein and its downstream signaling pathway play a major role in the interaction of this fungal pathogen and the host immune system.
Zdroje
1. Davis D, Edwards JE, Mitchell AP, Ibrahim AS. Candida albicans RIM101 pH response pathway is required for host-pathogen interactions. Infect Immun. 2000 Oct;68(10):5953–9. 10992507
2. Bertuzzi M, Schrettl M, Alcazar-Fuoli L, Cairns TC, Muñoz A, Walker LA, et al. The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis. PLoS Pathog. 2014 Oct 16;10(10):e1004413. doi: 10.1371/journal.ppat.1004413 25329394
3. O’Meara TR, Xu W, Selvig KM, O’Meara MJ, Mitchell AP, Alspaugh JA. The Cryptococcus neoformans Rim101 transcription factor directly regulates genes required for adaptation to the host. Mol Cell Biol. 2014 Feb 9;34(4):673–84. doi: 10.1128/MCB.01359-13 24324006
4. Huang W, Shang Y, Chen P, Gao Q, Wang C. MrpacC regulates sporulation, insect cuticle penetration and immune evasion in Metarhizium robertsii. Environ Microbiol. 2014 Mar 10;
5. Narayan S, Batta K, Colloby P, Tan CY. Cutaneous cryptococcus infection due to C. albidus associated with Sezary syndrome. Br J Dermatol. 2000;143(3):632–4. 10971343
6. You B-J, Choquer M, Chung K-R. The Colletotrichum acutatum gene encoding a putative pH-responsive transcription regulator is a key virulence determinant during fungal pathogenesis on citrus. Mol Plant Microbe Interact. 2007 Sep;20(9):1149–60. 17849717
7. Landraud P, Chuzeville S, Billon-Grande G, Poussereau N, Bruel C. Adaptation to pH and role of PacC in the rice blast fungus Magnaporthe oryzae. PLoS One. Public Library of Science; 2013 Jan 16;8(7):e69236. doi: 10.1371/journal.pone.0069236 23874922
8. Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS. 2009;23(4):525–30 doi: 10.1097/QAD.0b013e328322ffac 19182676
9. O’Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, et al. Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog. Public Library of Science; 2010 Feb;6(2):e1000776.
10. Chun CD, Madhani HD. Ctr2 links copper homeostasis to polysaccharide capsule formation and phagocytosis inhibition in the human fungal pathogen Cryptococcus neoformans. PLoS One. Public Library of Science; 2010;5(9):e12503.
11. O’Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA. Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. MBio. 2013 Jan;4(1).
12. Obara K, Yamamoto H, Kihara A. Membrane protein Rim21 plays a central role in sensing ambient pH in Saccharomyces cerevisiae. J Biol Chem. 2012 Nov 9;287(46):38473–81. doi: 10.1074/jbc.M112.394205 23019326
13. Herranz S, Rodríguez JM, Bussink H-J, Sánchez-Ferrero JC, Arst HN, Peñalva MA, et al. Arrestin-related proteins mediate pH signaling in fungi. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12141–6. 16099830
14. Galindo A, Calcagno-Pizarelli AM, Arst HN, Peñalva MÁ. An ordered pathway for the assembly of fungal ESCRT-containing ambient pH signalling complexes at the plasma membrane. J Cell Sci. 2012 Apr 1;125(Pt 7):1784–95. doi: 10.1242/jcs.098897 22344261
15. Calcagno-Pizarelli AM, Negrete-Urtasun S, Denison SH, Rudnicka JD, Bussink H-J, Múnera-Huertas T, et al. Establishment of the ambient pH signaling complex in Aspergillus nidulans: PalI assists plasma membrane localization of PalH. Eukaryot Cell. 2007 Dec 1;6(12):2365–75. 17951518
16. Barwell KJ, Boysen JH, Xu W, Aaron P, Mitchell AP. Relationship of DFG16 to the Rim101p pH Response Pathway in Saccharomyces cerevisiae and Candida albicans Relationship of DFG16 to the Rim101p pH Response Pathway in Saccharomyces cerevisiae and Candida albicans †. 2005;
17. Henne WM, Buchkovich NJ, Emr SD. The ESCRT pathway. Dev Cell. Elsevier Inc.; 2011 Jul 19;21(1):77–91.
18. Xu W, Smith FJ, Subaran R, Mitchell AP. Multivesicular body-ESCRT components function in pH response regulation in Saccharomyces cerevisiae and Candida albicans. Mol Biol Cell. 2004 Dec;15(12):5528–37. 15371534
19. Obara K, Kihara A. Signaling Events of the Rim101 Pathway Occur at the Plasma Membrane in a Ubiquitination-Dependent Manner. Mol Cell Biol. 2014 Sep 15;34 (18): 3525–34. doi: 10.1128/MCB.00408-14 25002535
20. Herrador A, Herranz S, Lara D, Vincent O. Recruitment of the ESCRT machinery to a putative seven-transmembrane-domain receptor is mediated by an arrestin-related protein. Mol Cell Biol. 2010 Feb 15;30(4):897–907. doi: 10.1128/MCB.00132-09 20028738
21. Peñalva MA, Lucena-Agell D, Arst HN. Liaison alcaline: Pals entice non-endosomal ESCRTs to the plasma membrane for pH signaling. Curr Opin Microbiol. 2014 Nov 1;22C:49–59.
22. Xu W, Mitchell AP. Yeast PalA / AIP1 / Alix Homolog Rim20p Associates with a PEST-Like Region and Is Required for Its Proteolytic Cleavage Yeast PalA / AIP1 / Alix Homolog Rim20p Associates with a PEST-Like Region and Is Required for Its Proteolytic Cleavage. 2001;183(23). 11698381
23. Díez E, Alvaro J, Espeso E a, Rainbow L, Suárez T, Tilburn J, et al. Activation of the Aspergillus PacC zinc finger transcription factor requires two proteolytic steps. EMBO J. 2002 Mar 15;21(6):1350–9. 11889040
24. Davis DA. How human pathogenic fungi sense and adapt to pH: the link to virulence. Curr Opin Microbiol. 2009/07/28 ed. 2009;12(4):365–70. doi: 10.1016/j.mib.2009.05.006 19632143
25. Aréchiga-Carvajal ET, Ruiz-Herrera J. The RIM101/pacC Homologue from the Basidiomycete Ustilago maydis Is Functional in Multiple pH-Sensitive Phenomena. Eukaryot Cell. 2005 Jun;4(6):999–1008. 15947192
26. Antonio C-CJ, Lucila O-C, Miriam T-S, Scott G, José R-H. Functional analysis of the pH responsive pathway Pal/Rim in the phytopathogenic basidiomycete Ustilago maydis. Fungal Genet Biol. 2010;47(5):446–57. doi: 10.1016/j.fgb.2010.02.004 20153837
27. Kosman DJ. Iron metabolism in aerobes: Managing ferric iron hydrolysis and ferrous iron autoxidation. Coordination Chemistry Reviews. 2013. p. 210–7.
28. Li W, Mitchell AP. Proteolytic Activation of Rim1p, a Positive Regulator of Yeast Sporulation and Invasive Growth. Genetics. 1997;145(1):63–73. 9017390
29. Orejas M, Espeso EA, Tilburn J, Sarkar S, Arst HN Jr., Penalva MA. Activation of the Aspergillus PacC transcription factor in response to alkaline ambient pH requires proteolysis of the carboxy-terminal moiety. Genes Dev. 1995/07/01 ed. 1995;9(13):1622–32. 7628696
30. Kullas AL, Li M, Davis DA. Snf7p, a component of the ESCRT-III protein complex, is an upstream member of the RIM101 pathway in Candida albicans. Eukaryot Cell. 2004 Dec;3(6):1609–18. 15590834
31. Blanchin-Roland S, Da Costa G, Gaillardin C. ESCRT-I components of the endocytic machinery are required for Rim101-dependent ambient pH regulation in the yeast Yarrowia lipolytica. Microbiology. 2005 Nov;151(Pt 11):3627–37. 16272384
32. Rodríguez-Galán O, Galindo A, Hervás-Aguilar A, Arst HN, Peñalva MA. Physiological involvement in pH signaling of Vps24-mediated recruitment of Aspergillus PalB cysteine protease to ESCRT-III. J Biol Chem. 2009 Feb 13;284(7):4404–12. doi: 10.1074/jbc.M808645200 19056728
33. Calcagno-Pizarelli AM, Hervás-Aguilar A, Galindo A, Abenza JF, Peñalva MA, Arst HN. Rescue of Aspergillus nidulans severely debilitating null mutations in ESCRT-0, I, II and III genes by inactivation of a salt-tolerance pathway allows examination of ESCRT gene roles in pH signalling. J Cell Sci. 2011 Dec 1;124(Pt 23):4064–76. doi: 10.1242/jcs.088344 22135362
34. Hu G, Caza M, Cadieux B, Chan V, Liu V, Kronstad J. Cryptococcus neoformans requires the ESCRT protein Vps23 for iron acquisition from heme, for capsule formation, and for virulence. Infect Immun. 2013;81(1):292–302. doi: 10.1128/IAI.01037-12 23132495
35. Chun CD, Madhani HD. Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans. PLoS One. Public Library of Science; 2010;5(9):e12503.
36. Godinho RM da C, Crestani J, Kmetzsch L, Araujo G de S, Frases S, Staats CC, et al. The vacuolar-sorting protein Snf7 is required for export of virulence determinants in members of the Cryptococcus neoformans complex. Sci Rep. Nature Publishing Group; 2014 Jan 2;4 : 6198. doi: 10.1038/srep06198 25178636
37. Jung WH, Saikia S, Hu G, Wang J, Fung CK, D’Souza C, et al. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans. PLoS Pathog. 2010;6(11):e1001209. doi: 10.1371/journal.ppat.1001209 21124817
38. Hofmann K, Stoffel W. TMBASE—a database of membrane spanning protein segments. Biol Chem HoppeSeyler. 1993;374 : 166.
39. Alspaugh JA, Perfect JR, Heitman J. Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 andcAMP. Genes Dev. 1997;11(23):3206–17. 9389652
40. Hsueh Y-PP, Xue C, Heitman J. G protein signaling governing cell fate decisions involves opposing Galpha subunits in Cryptococcus neoformans. Mol Biol Cell. 2007 Sep 1;18(9):3237–49. 17581859
41. Okagaki LH, Strain AK, Nielsen JN, Charlier C, Baltes NJ, Chrétien F, et al. Cryptococcal Cell Morphology Affects Host Cell Interactions and Pathogenicity. PLoS Pathog. Public Library of Science; 2010;6(6):e1000953.
42. Zaragoza O, García-Rodas R, Nosanchuk JD, Cuenca-Estrella M, Rodríguez-Tudela JL, Casadevall A. Fungal Cell Gigantism during Mammalian Infection. PLoS Pathog. Public Library of Science; 2010;6(6):e1000945.
43. Okagaki LH, Wang Y, Ballou ER, O’Meara TR, Bahn Y-SS, Alspaugh JA, et al. Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli. Eukaryot Cell. 2011 Oct;10(10):1306–16. doi: 10.1128/EC.05179-11 21821718
44. Ikeda M, Kihara A, Denpoh A, Igarashi Y. The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry. 2008;19(May):1922–31. doi: 10.1091/mbc.E07-08-0806 18287536
45. Da C. Godinho RM, Crestani J, Kmetzsch L, de S. Araujo G, Frases S, Staats CC, et al. The vacuolar-sorting protein Snf7 is required for export of virulence determinants in members of the Cryptococcus neoformans complex. Sci Rep. Macmillan Publishers Limited. All rights reserved; 2014 Sep 2;4.
46. Chun CD, Madhani HD. Ctr2 links copper homeostasis to polysaccharide capsule formation and phagocytosis inhibition in the human fungal pathogen Cryptococcus neoformans. PLoS One. 2010;5(9).
47. Ludwig M-G, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, et al. Proton-sensing G-protein-coupled receptors. Nature. Nature Publishing Group; 2003 Sep 4;425(6953):93–8. 12955148
48. Krulwich TA, Sachs G, Padan E. Molecular aspects of bacterial pH sensing and homeostasis. Nat Rev Microbiol. 2011;9 : 330–43. doi: 10.1038/nrmicro2549 21464825
49. Levin LR, Buck J. Physiological Roles of Acid-Base Sensors. Annu Rev Physiol. Annual Reviews; 2015 Feb 10;77(1):347–62.
50. Harrison JS, Higgins CD, O’Meara MJ, Koellhoffer JF, Kuhlman BA, Lai JR. Role of electrostatic repulsion in controlling pH-dependent conformational changes of viral fusion proteins. Structure. Elsevier Ltd; 2013 Jul 2;21(7):1085–96. doi: 10.1016/j.str.2013.05.009 23823327
51. Heath VL, Shaw SL, Roy S, Cyert S, Heath VL, Shaw SL, et al. Hph1p and Hph2p, Novel Components of Calcineurin-Mediated Stress Responses in Saccharomyces cerevisiae Hph1p and Hph2p, Novel Components of Calcineurin-Mediated Stress Responses in Saccharomyces cerevisiae. 2004;
52. Dechant R, Saad S, Ibáñez AJ, Peter M. Cytosolic pH regulates cell growth through distinct GTPases, Arf1 and Gtr1, to promote Ras/PKA and TORC1 activity. Mol Cell. 2014 Aug 7;55(3):409–21. doi: 10.1016/j.molcel.2014.06.002 25002144
53. Chen Y, Toffaletti DL, Tenor JL. The Cryptococcus neoformans Transcriptome at the Site of Human. 2014;
54. Janbon G, Ormerod KL, Paulet D, Byrnes EJ, Yadav V, Chatterjee G, et al. Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation. PLoS Genet. 2014 Apr;10(4):e1004261. doi: 10.1371/journal.pgen.1004261 24743168
55. Sherman F. Getting started with yeast. Methods Enzym. 1991;194 : 3–41. 2005794
56. Murashige T, Skoog F. A Revised Medium for Rapid Growth and Bio Assays with Tobacco Tissue Cultures. Physiol Plant. Blackwell Publishing Ltd; 1962;15(3):473–97.
57. Perfect JR, Lang SD, Durack DT. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am J Pathol. 1980;101(1):177–94. 7004196
58. Nielsen K, Cox GM, Wang P, Toffaletti DL, Perfect JR, Heitman J. Sexual cycle of Cryptococcus neoformans var. grubii and Virulence of congenic a and α isolates. Infect Immun. 2003;71(9):4831–41. 12933823
59. Xue C, Bahn Y-SS, Cox GM, Heitman J. G Protein-coupled Receptor Gpr4 Senses Amino Acids and Activates the cAMP-PKA Pathway in Cryptococcus neoformans. Mol Biol Cell. 2006;17(2):667–79. 16291861
60. Kidd SE, Hagen F, Tscharke RL, Huynh M, Bartlett KH, Fyfe M, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci U S A. 2004;101(49):17258–63. 15572442
61. Fraser JA, Subaran RL, Nichols CB, Heitman J. Recapitulation of the Sexual Cycle of the Primary Fungal Pathogen Cryptococcus neoformans var. gattii: Implications for an Outbreak on Vancouver Island, Canada. Eukaryot Cell. 2003;2(5):1036–45. 14555486
62. Toffaletti DL, Rude TH, Johnston SA, Durack DT, Perfect JR. Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA. J Bacteriol. 1993;175(5):1405–11. 8444802
63. Kim MS, Kim SY, Jung KW, Bahn YS. Targeted gene disruption in Cryptococcus neoformans using double-joint PCR with split dominant selectable markers. Methods Mol Biol. 2012;845 : 67–84. doi: 10.1007/978-1-61779-539-8_5 22328368
64. Price MS, Nichols CB, Alspaugh JA. The Cryptococcus neoformans Rho-GDP Dissociation Inhibitor Mediates Intracellular Survival and Virulence. Infect Immun. 2008;76(12):5729–37. doi: 10.1128/IAI.00896-08 18779335
65. Idnurm A, Reedy JL, Nussbaum JC, Heitman J. Cryptococcus neoformans virulence gene discovery through insertional mutagenesis. Eukaryot Cell. 2004 Apr 9;3(2):420–9. 15075272
66. Nichols CB, Ferreyra J, Ballou ER, Alspaugh JA. Subcellular localization directs signaling specificity of the Cryptococcus neoformans Ras1 protein. Eukaryot Cell. 2009;8(2):181–9. doi: 10.1128/EC.00351-08 19098128
67. Cox GM, Mukherjee J, Cole GT, Casadevall A, Perfect JR. Urease as a Virulence Factor in Experimental Cryptococcosis. Infect Immun. 2000;68(2):443–8. 10639402
68. Notredame C, Higgins DG, Heringa J. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol. 2000;302 : 205–17. 10964570
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