The Cryptococcus neoformans Rim101 Transcription Factor Directly Regulates Genes Required for Adaptation to the Host

REFERENCES

• Alspaugh J, Perfect J, Heitman J. 1998. Signal transduction pathways regulating differentiation and pathogenicity of Cryptococcus neoformans. Fungal Genet. Biol. 25:1–14. http://dx.doi.org/10.1006/fgbi.1998.1079.
   PubMedGoogle Scholar
• O'Meara TR, Alspaugh JA. 2012. The Cryptococcus neoformans capsule: a sword and a shield. Clin. Microbiol. Rev. 25:387–408. http://dx.doi.org/10.1128/CMR.00001-12.
   PubMed Web of Science ®Google Scholar
• Dykstra MA, Friedman L, Murphy JW. 1977. Capsule size of Cryptococcus neoformans: control and relationship to virulence. Infect. Immun. 16:129–135.
   PubMed Web of Science ®Google Scholar
• Kozel T, Gotschlich E. 1982. The capsule of Cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J. Immunol. 129:1675–1680.
   PubMed Web of Science ®Google Scholar
• Chang YC, Kwon-Chung KJ. 1994. Complementation of a capsule-deficient mutation of Cryptococcus neoformans restores its virulence. Mol. Cell. Biol. 14:4912–4919.
   PubMed Web of Science ®Google Scholar
• Chang YC, Penoyer LA, Kwon-Chung KJ. 1996. The second capsule gene of Cryptococcus neoformans, CAP64, is essential for virulence. Infect. Immun. 64:1977–1983.
   PubMed Web of Science ®Google Scholar
• Doering TL. 2009. How sweet it is! Cell wall biogenesis and polysaccharide capsule formation in Cryptococcus neoformans. Annu. Rev. Microbiol. 63:223–247. http://dx.doi.org/10.1146/annurev.micro.62.081307.162753.
   PubMed Web of Science ®Google Scholar
• O'Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, Alspaugh JA. 2010. Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule. PLoS Pathog. 6:e1000776. http://dx.doi.org/10.1371/journal.ppat.1000776.
   PubMed Web of Science ®Google Scholar
• O'Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA. 2013. Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses. mBio 4(1):e00522–12. http://dx.doi.org/10.1128/mBio.00522-12.
   PubMedGoogle Scholar
• Caddick MX, Brownlee AG, Arst HN. 1986. Regulation of gene expression by pH of the growth medium in Aspergillus nidulans. Mol. Gen. Genet. 203:346–353. http://dx.doi.org/10.1007/BF00333978.
   PubMedGoogle Scholar
• Su SSY, Mitchell AP. 1993. Molecular characterization of the yeast meiotic regulatory gene RIM1. Nucleic Acids Res. 21:3789–3797. http://dx.doi.org/10.1093/nar/21.16.3789.
   PubMed Web of Science ®Google Scholar
• Li W, Mitchell AP. 1997. Proteolytic activation of Rim1p, a positive regulator of yeast sporulation and invasive growth. Genetics 145:63–73.
   PubMed Web of Science ®Google Scholar
• Lamb T, Xu W, Diamond A, Mitchell AP. 2001. Alkaline response genes of Saccharomyces cerevisiae and their relationship to the RIM101 pathway. J. Biol. Chem. 276:1850–1856. http://dx.doi.org/10.1074/jbc.M008381200.
   PubMed Web of Science ®Google Scholar
• Herranz S, Rodriguez JM, Bussink H-J, Sanchez-Ferrero JC, Arst HNJr, Penalva MA, Vincent O. 2005. Arrestin-related proteins mediate pH signaling in fungi. Proc. Natl. Acad. Sci. U. S. A. 102:12141–12146. http://dx.doi.org/10.1073/pnas.0504776102.
   PubMed Web of Science ®Google Scholar
• Calcagno-Pizarelli AM, Negrete-Urtasun S, Denison SH, Rudnicka JD, Bussink H-J, Munera-Huertas T, Stanton L, Hervás-Aguilar A, Espeso EA, Tilburn J, Arst HNJr, Peñalva MA. 2007. Establishment of the ambient pH signaling complex in Aspergillus nidulans: PalI assists plasma membrane localization of PalH. Eukaryot. Cell 6:2365–2375. http://dx.doi.org/10.1128/EC.00275-07.
   PubMed Web of Science ®Google Scholar
• Galindo A, Hervás-Aguilar A, Rodríguez-Galán O, Vincent O, Arst HNJr, Tilburn J, Peñalva MA. 2007. PalC, one of two Bro1 domain proteins in the fungal pH signalling pathway, localizes to cortical structures and binds Vps32. Traffic 8:1346–1364. http://dx.doi.org/10.1111/j.1600-0854.2007.00620.x.
   PubMed Web of Science ®Google Scholar
• Cornet M, Bidard F, Schwarz P, Da Costa G, Blanchin-Roland S, Dromer F, Gaillardin C. 2005. Deletions of endocytic components VPS28 and VPS32 affect growth at alkaline pH and virulence through both RIM101-dependent and RIM101-independent pathways in Candida albicans. Infect. Immun. 73:7977–7987. http://dx.doi.org/10.1128/IAI.73.12.7977-7987.2005.
   PubMed Web of Science ®Google Scholar
• Hayashi M, Fukuzawa T, Sorimachi H, Maeda T. 2005. Constitutive activation of the pH-responsive Rim101 pathway in yeast mutants defective in late steps of the MVB/ESCRT pathway. Mol. Cell. Biol. 25:9478–9490. http://dx.doi.org/10.1128/MCB.25.21.9478-9490.2005.
   PubMedGoogle Scholar
• Rothfels K, Tanny JC, Molnar E, Friesen H, Commisso C, Segall J. 2005. Components of the ESCRT pathway, DFG16, and YGR122w are required for Rim101 to act as a corepressor with Nrg1 at the negative regulatory element of the DIT1 gene of Saccharomyces cerevisiae. Mol. Cell. Biol. 25:6772–6788. http://dx.doi.org/10.1128/MCB.25.15.6772-6788.2005.
   PubMedGoogle Scholar
• Herrador A, Herranz S, Lara D, Vincent O. 2010. Recruitment of the ESCRT machinery to a putative seven-transmembrane-domain receptor is mediated by an arrestin-related protein. Mol. Cell. Biol. 30:897–907. http://dx.doi.org/10.1128/MCB.00132-09.
   PubMedGoogle Scholar
• Li M, Martin SJ, Bruno VM, Mitchell AP, Davis DA. 2004. Candida albicans Rim13p, a protease required for Rim101p processing at acidic and alkaline pHs. Eukaryot. Cell 3:741–751. http://dx.doi.org/10.1128/EC.3.3.741-751.2004.
   PubMedGoogle Scholar
• Mingot JM, Espeso EA, Diez E, Penalva MA. 2001. Ambient pH signaling regulates nuclear localization of the Aspergillus nidulans PacC transcription factor. Mol. Cell. Biol. 21:1688–1699. http://dx.doi.org/10.1128/MCB.21.5.1688-1699.2001.
   PubMed Web of Science ®Google Scholar
• Cadieux B, Lian T, Hu G, Wang J, Biondo C, Teti G, Liu V, Murphy MEP, Creagh AL, Kronstad JW. 2013. The mannoprotein Cig1 supports iron acquisition from heme and virulence in the pathogenic fungus Cryptococcus neoformans. J. Infect. Dis. 207:1339–1347. http://dx.doi.org/10.1093/infdis/jit029.
   PubMed Web of Science ®Google Scholar
• Jung WH, Saikia S, Hu G, Wang J, Fung CK-Y, D'Souza C, White R, Kronstad JW. 2010. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans. PLoS Pathog. 6:e1001209. http://dx.doi.org/10.1371/journal.ppat.1001209.
   PubMed Web of Science ®Google Scholar
• Aréchiga-Carvajal E, Ruiz-Herrera J. 2005. The RIM101/pacC homologue from the basidiomycete Ustilago maydis is functional in multiple pH-sensitive phenomena. Eukaryot. Cell 4:999–1008. http://dx.doi.org/10.1128/EC.4.6.999-1008.2005.
   PubMed Web of Science ®Google Scholar
• Davis D, Wilson RB, Mitchell AP. 2000. RIM101-dependent and -independent pathways govern pH responses in Candida albicans. Mol. Cell. Biol. 20:971–978. http://dx.doi.org/10.1128/MCB.20.3.971-978.2000.
   PubMed Web of Science ®Google Scholar
• Davis D. 2003. Adaptation to environmental pH in Candida albicans and its relation to pathogenesis. Curr. Genet. 44:1–7. http://dx.doi.org/10.1007/s00294-003-0415-2.
   PubMed Web of Science ®Google Scholar
• Bensen E, Martin SJ, Li M, Berman J, Davis DA. 2004. Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p. Mol. Microbiol. 54:1335–1351. http://dx.doi.org/10.1111/j.1365-2958.2004.04350.x.
   PubMed Web of Science ®Google Scholar
• Espeso EA, Tilburn J, Arst HNJr, Penalva MA. 1993. pH regulation is a major determinant in expression of a fungal penicillin biosynthetic gene. EMBO J. 12:3947–3956.
   PubMedGoogle Scholar
• Tilburn J, Sarkar S, Widdick DA, Espeso EA, Orejas M, Mungroo J, Penalva MA, Arst HNJr. 1995. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 14:779–790.
   PubMed Web of Science ®Google Scholar
• Peñalva MA, Tilburn J, Bignell E, Arst HNJr. 2008. Ambient pH gene regulation in fungi: making connections. Trends Microbiol. 16:291–300. http://dx.doi.org/10.1016/j.tim.2008.03.006.
   PubMed Web of Science ®Google Scholar
• Ramón AM, Fonzi WA. 2003. Diverged binding specificity of Rim101p, the Candida albicans ortholog of PacC. Eukaryot. Cell 2:718–728. http://dx.doi.org/10.1128/EC.2.4.718-728.2003.
   PubMedGoogle Scholar
• Lamb TM, Mitchell AP. 2003. The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae. Mol. Cell. Biol. 23:677–686. http://dx.doi.org/10.1128/MCB.23.2.677-686.2003.
   PubMed Web of Science ®Google Scholar
• Baek Y, Li M, Davis D. 2008. Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors. Eukaryot. Cell 7:1168–1179. http://dx.doi.org/10.1128/EC.00108-08.
   PubMedGoogle Scholar
• Baek Y-U, Martin SJ, Davis DA. 2006. Evidence for novel pH-dependent regulation of Candida albicans Rim101, a direct transcriptional repressor of the cell wall beta-glycosidase Phr2. Eukaryot. Cell 5:1550–1559. http://dx.doi.org/10.1128/EC.00088-06.
   PubMedGoogle Scholar
• Espeso EA, Penalva MA. 1996. Three binding sites for the Aspergillus nidulans PacC zinc-finger transcription factor are necessary and sufficient for regulation by ambient pH of the isopenicillin N synthase gene promoter. J. Biol. Chem. 271:28825–28830. http://dx.doi.org/10.1074/jbc.271.46.28825.
   PubMedGoogle Scholar
• Trapnell C, Pachter L, Salzberg SL. 2009. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25:1105–1111. http://dx.doi.org/10.1093/bioinformatics/btp120.
   PubMed Web of Science ®Google Scholar
• Cramer KL, Gerrald QD, Nichols CB, Price MS, Alspaugh JA. 2006. Transcription factor Nrg1 mediates capsule formation, stress response, and pathogenesis in Cryptococcus neoformans. Eukaryot. Cell 5:1147–1156. http://dx.doi.org/10.1128/EC.00145-06.
   PubMedGoogle Scholar
• Chun CD, Brown JCS, Madhani HD. 2011. A major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by Cryptococcus neoformans. Cell Host Microbe 9:243–251. http://dx.doi.org/10.1016/j.chom.2011.02.003.
   PubMedGoogle Scholar
• Schmittgen TD, Livak KJ. 2008. Analyzing real-time PCR data by the comparative CT method. Nat. Protoc. 3:1101–1108. http://dx.doi.org/10.1038/nprot.2008.73.
   PubMed Web of Science ®Google Scholar
• Chang YC, Lamichhane AK, Kwon-Chung KJ. 2012. Role of actin-bundling protein Sac6 in growth of Cryptococcus neoformans at low oxygen concentration. Eukaryot. Cell 11:943–951. http://dx.doi.org/10.1128/EC.00120-12.
   PubMedGoogle Scholar
• Shedletzky E, Unger C, Delmer DP. 1997. A microtiter-based fluorescence assay for (1,3)-β-glucan synthases. Anal. Biochem. 249:88–93. http://dx.doi.org/10.1006/abio.1997.2162.
   PubMed Web of Science ®Google Scholar
• Fox DS, Cox GM, Heitman J. 2003. Phospholipid-binding protein Cts1 controls septation and functions coordinately with calcineurin in Cryptococcus neoformans. Eukaryot. Cell 2:1025–1035. http://dx.doi.org/10.1128/EC.2.5.1025-1035.2003.
   PubMedGoogle Scholar
• Fanning S, Xu W, Solis N, Woolford CA, Filler SG, Mitchell AP. 2012. Divergent targets of Candida albicans biofilm regulator Bcr1 in vitro and in vivo. Eukaryot. Cell 11:896–904. http://dx.doi.org/10.1128/EC.00103-12.
   PubMedGoogle Scholar
• Boj SF, Petrov D, Ferrer J. 2010. Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1a and Hnf4a. PLoS Genet. 6:e1000970. http://dx.doi.org/10.1371/journal.pgen.1000970.
   PubMedGoogle Scholar
• Fanning S, Xu W, Beaurepaire C, Suhan JP, Nantel A, Mitchell AP. 2012. Functional control of the Candida albicans cell wall by catalytic protein kinase A subunit Tpk1. Mol. Microbiol. 86:284–302. http://dx.doi.org/10.1111/j.1365-2958.2012.08193.x.
   PubMed Web of Science ®Google Scholar
• Baker LG, Specht CA, Donlin MJ, Lodge JK. 2007. Chitosan, the deacetylated form of chitin, is necessary for cell wall integrity in Cryptococcus neoformans. Eukaryot. Cell 6:855–867. http://dx.doi.org/10.1128/EC.00399-06.
   PubMed Web of Science ®Google Scholar
• Baker LG, Specht CA, Lodge JK. 2009. Chitinases are essential for sexual development but not vegetative growth in Cryptococcus neoformans. Eukaryot. Cell 8:1692–1705. http://dx.doi.org/10.1128/EC.00227-09.
   PubMedGoogle Scholar
• Baker LG, Specht CA, Lodge JK. 2011. Cell wall chitosan is necessary for virulence in the opportunistic pathogen Cryptococcus neoformans. Eukaryot. Cell 10:1264–1268. http://dx.doi.org/10.1128/EC.05138-11.
   PubMedGoogle Scholar
• Banks IR, Specht CA, Donlin MJ, Gerik KJ, Levitz SM, Lodge JK. 2005. A chitin synthase and its regulator protein are critical for chitosan production and growth of the fungal pathogen Cryptococcus neoformans. Eukaryot. Cell 4:1902–1912. http://dx.doi.org/10.1128/EC.4.11.1902-1912.2005.
   PubMedGoogle Scholar
• Xu W, Mitchell AP. 2001. Yeast PalA/AIP1/Alix homolog Rim20p associates with a PEST-like region and is required for its proteolytic cleavage. J. Bacteriol. 183:6917–6923. http://dx.doi.org/10.1128/JB.183.23.6917-6923.2001.
   PubMed Web of Science ®Google Scholar
• Idnurm A, Walton FJ, Floyd A, Reedy JL, Heitman J. 2009. Identification of ENA1 as a virulence gene of the human pathogenic fungus Cryptococcus neoformans through signature-tagged insertional mutagenesis. Eukaryot. Cell 8:315–326. http://dx.doi.org/10.1128/EC.00375-08.
   PubMed Web of Science ®Google Scholar
• Jung WH, Sham A, Lian T, Singh A, Kosman DJ, Kronstad JW. 2008. Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog. 4:e45. http://dx.doi.org/10.1371/journal.ppat.0040045.
   PubMed Web of Science ®Google Scholar
• O'Meara TR, Hay C, Price MS, Giles S, Alspaugh JA. 2010. Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host. Eukaryot. Cell 9:1193–1202. http://dx.doi.org/10.1128/EC.00098-10.
   PubMedGoogle Scholar
• Ko Y-J, Yu YM, Kim G-B, Lee G-W, Maeng PJ, Kim S, Floyd A, Heitman J, Bahn Y-S. 2009. Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways. Eukaryot. Cell 8:1197–1217. http://dx.doi.org/10.1128/EC.00120-09.
   PubMedGoogle Scholar
• Haynes BC, Skowyra ML, Spencer SJ, Gish SR, Williams M, Held EP, Brent MR, Doering TL. 2011. Toward an integrated model of capsule regulation in Cryptococcus neoformans. PLoS Pathog. 7:e1002411. http://dx.doi.org/10.1371/journal.ppat.1002411.
   PubMed Web of Science ®Google Scholar
• Caracuel Z, Roncero MIG, Espeso EA, González-Verdejo CI, García-Maceira FI, Di Pietro A. 2003. The pH signalling transcription factor PacC controls virulence in the plant pathogen Fusarium oxysporum. Mol. Microbiol. 48:765–779. http://dx.doi.org/10.1046/j.1365-2958.2003.03465.x.
   PubMed Web of Science ®Google Scholar
• Peñas MM, Hervas-Aguilar A, Munera-Huertas T, Reoyo E, Penalva MA, Arst HNJr, Tilburn J. 2007. Further characterization of the signaling proteolysis step in the Aspergillus nidulans pH signal transduction pathway. Eukaryot. Cell 6:960–970. http://dx.doi.org/10.1128/EC.00047-07.
   PubMedGoogle Scholar
• Pukkila-Worley R, Gerrald QD, Kraus PR, Boily M-J, Davis MJ, Giles SS, Cox GM, Heitman J, Alspaugh JA. 2005. Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade. Eukaryot. Cell 4:190–201. http://dx.doi.org/10.1128/EC.4.1.190-201.2005.
   PubMedGoogle Scholar
• Jung K-W, Strain AK, Nielsen K, Jung K-H, Bahn Y-S. 2012. 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. 49:332–345. http://dx.doi.org/10.1016/j.fgb.2012.02.001.
   PubMed Web of Science ®Google Scholar
• D'Souza CA, Alspaugh JA, Yue C, Harashima T, Cox GM, Perfect JR, Heitman J. 2001. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol. 21:3179–3191. http://dx.doi.org/10.1128/MCB.21.9.3179-3191.2001.
   PubMed Web of Science ®Google Scholar
• Hu G, Steen BR, Lian T, Sham AP, Tam N, Tangen KL, Kronstad JW. 2007. Transcriptional regulation by protein kinase A in Cryptococcus neoformans. PLoS Pathog. 3:e42. http://dx.doi.org/10.1371/journal.ppat.0030042.
   PubMedGoogle Scholar
• Nobile CJ, Solis N, Myers CL, Fay AJ, Deneault J-S, Nantel A, Mitchell AP, Filler SG. 2008. Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions. Cell. Microbiol. 10:2180–2196. http://dx.doi.org/10.1111/j.1462-5822.2008.01198.x.
   PubMed Web of Science ®Google Scholar
• Villar CC, Kashleva H, Nobile CJ, Mitchell AP, Dongari-Bagtzoglou A. 2007. Mucosal tissue invasion by Candida albicans is associated with E-cadherin degradation, mediated by transcription factor Rim101p and protease Sap5p. Infect. Immun. 75:2126–2135. http://dx.doi.org/10.1128/IAI.00054-07.
   PubMed Web of Science ®Google Scholar
• Castrejon F, Gomez A, Sanz M, Duran A, Roncero C. 2006. The RIM101 pathway contributes to yeast cell wall assembly and its function becomes essential in the absence of mitogen-activated protein kinase Slt2p. Eukaryot. Cell 5:507–517. http://dx.doi.org/10.1128/EC.5.3.507-517.2006.
   PubMedGoogle Scholar
• Espeso EA, Arst HN. 2000. On the mechanism by which alkaline pH prevents expression of an acid-expressed gene. Mol. Cell. Biol. 20:3355–3363. http://dx.doi.org/10.1128/MCB.20.10.3355-3363.2000.
   PubMed Web of Science ®Google Scholar
• Lee A, Toffaletti DL, Tenor J, Soderblom EJ, Thompson JW, Moseley MA, Price M, Perfect JR. 2010. Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis. Infect. Immun. 78:4213–4225. http://dx.doi.org/10.1128/IAI.00551-10.
   PubMed Web of Science ®Google Scholar
• Ding C, Festa RA, Chen Y-L, Espart A, Palacios O, Espin J, Capdevila M, Atrian S, Heitman J, Thiele DJ. 2013. Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence. Cell Host Microbe 13:265–276. http://dx.doi.org/10.1016/j.chom.2013.02.002.
   PubMed Web of Science ®Google Scholar