Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Review Article

The Regulatory Function of the Molecular Chaperone Hsp90 in the Cell Wall Integrity of Pathogenic Fungi

Author(s): Marina Campos Rocha, Camilla Alves Santos and Iran Malavazi*

Volume 16, Issue 1, 2019

Page: [44 - 53] Pages: 10

DOI: 10.2174/1570164615666180820155807

Price: $65

Abstract

Different signaling cascades including the Cell Wall Integrity (CWI), the High Osmolarity Glycerol (HOG) and the Ca2+/calcineurin pathways control the cell wall biosynthesis and remodeling in fungi. Pathogenic fungi, such as Aspergillus fumigatus and Candida albicans, greatly rely on these signaling circuits to cope with different sources of stress, including the cell wall stress evoked by antifungal drugs and the host’s response during infection. Hsp90 has been proposed as an important regulatory protein and an attractive target for antifungal therapy since it stabilizes major effector proteins that act in the CWI, HOG and Ca2+/calcineurin pathways. Data from the human pathogen C. albicans have provided solid evidence that loss-of-function of Hsp90 impairs the evolution of resistance to azoles and echinocandin drugs. In A. fumigatus, Hsp90 is also required for cell wall integrity maintenance, reinforcing a coordinated function of the CWI pathway and this essential molecular chaperone. In this review, we focus on the current information about how Hsp90 impacts the aforementioned signaling pathways and consequently the homeostasis and maintenance of the cell wall, highlighting this cellular event as a key mechanism underlying antifungal therapy based on Hsp90 inhibition.

Keywords: Cell wall integrity, heat shock, Hsp90, Aspergillus fumigatus, Candida albicans, chitin.

Graphical Abstract
[1]
Brown, G.D.; Denning, D.W.; Gow, N.A.; Levitz, S.M.; Netea, M.G.; White, T.C. Hidden killers: Human fungal infections. Sci. Transl. Med., 2012, 4(165), 165rv13.
[2]
Brown, G.D.; Meintjes, G.; Kolls, J.K.; Gray, C.; Horsnell, W.; Achan, B.; Alber, G.; Aloisi, M.; Armstrong-James, D.; Beale, M.; Bicanic, T.; Black, J.; Bohjanen, P.; Botes, A.; Boulware, D.R.; Brown, G.; Bunjun, R.; Carr, W.; Casadevall, A.; Chang, C.; Chivero, E.; Corcoran, C.; Cross, A.; Dawood, H.; Day, J.; De Bernardis, F.; De Jager, V.; De Repentigny, L.; Denning, D.; Eschke, M.; Finkelman, M.; Govender, N.; Gow, N.; Graham, L.; Gryschek, R.; Hammond-Aryee, K.; Harrison, T.; Heard, N.; Hill, M.; Hoving, J.C.; Janoff, E.; Jarvis, J.; Kayuni, S.; King, K.; Kolls, J.; Kullberg, B.J.; Lalloo, D.G.; Letang, E.; Levitz, S.; Limper, A.; Longley, N.; Machiridza, T.R.; Mahabeer, Y.; Martinsons, N.; Meiring, S.; Meya, D.; Miller, R.; Molloy, S.; Morris, L.; Mukaremera, L.; Musubire, A.K.; Muzoora, C.; Nair, A.; Nakiwala Kimbowa, J.; Netea, M.; Nielsen, K.; O’Hern, J.; Okurut, S.; Parker, A.; Patterson, T.; Pennap, G.; Perfect, J.; Prinsloo, C.; Rhein, J.; Rolfes, M.A.; Samuel, C.; Schutz, C.; Scriven, J.; Sebolai, O.M.; Sojane, K.; Sriruttan, C.; Stead, D.; Steyn, A.; Thawer, N.K.; Thienemann, F.; Von Hohenberg, M.; Vreulink, J.M.; Wessels, J.; Wood, K.; Yang, Y.L. AIDS-related mycoses: The way forward. Trends Microbiol., 2014, 22(3), 107-109.
[3]
Cowen, L.E.; Singh, S.D.; Kohler, J.R.; Collins, C.; Zaas, A.K.; Schell, W.A.; Aziz, H.; Mylonakis, E.; Perfect, J.R.; Whitesell, L.; Lindquist, S. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proc. Natl. Acad. Sci. USA, 2009, 106(8), 2818-2823.
[4]
O’Meara, T.R.; Cowen, L.E. Hsp90-dependent regulatory circuitry controlling temperature-dependent fungal development and virulence. Cell. Microbiol., 2014, 16(4), 473-481.
[5]
Veri, A.; Cowen, L.E. Progress and prospects for targeting Hsp90 to treat fungal infections. Parasitology, 2014, 141(9), 1127-1137.
[6]
Leach, M.D.; Farrer, R.A.; Tan, K.; Miao, Z.; Walker, L.A.; Cuomo, C.A.; Wheeler, R.T.; Brown, A.J.; Wong, K.H.; Cowen, L.E. Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans. Nat. Commun., 2016, 7, 11704.
[7]
Klinkert, B.; Narberhaus, F. Microbial thermosensors. Cell. Mol. Life Sci., 2009, 66(16), 2661-2676.
[8]
Nicholls, S.; MacCallum, D.M.; Kaffarnik, F.A.; Selway, L.; Peck, S.C.; Brown, A.J. Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans. Fungal Genet. Biol., 2011, 48(3), 297-305.
[9]
Shapiro, R.S.; Uppuluri, P.; Zaas, A.K.; Collins, C.; Senn, H.; Perfect, J.R.; Heitman, J.; Cowen, L.E. Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr. Biol., 2009, 19(8), 621-629.
[10]
Truman, A.W.; Millson, S.H.; Nuttall, J.M.; Mollapour, M.; Prodromou, C.; Piper, P.W. In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity. Eukaryot. Cell, 2007, 6(4), 744-752.
[11]
Chen, Y.L.; Brand, A.; Morrison, E.L.; Silao, F.G.; Bigol, U.G.; Malbas, F.F. Jr.; Nett, J.E.; Andes, D.R.; Solis, N.V.; Filler, S.G.; Averette, A.; Heitman, J. Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis. Eukaryot. Cell, 2011, 10(6), 803-819.
[12]
Cooney, N.M.; Klein, B.S. Fungal adaptation to the mammalian host: It is a new world, after all. Curr. Opin. Microbiol., 2008, 11(6), 511-516.
[13]
Leach, M.D.; Klipp, E.; Cowen, L.E.; Brown, A.J. Fungal Hsp90: A biological transistor that tunes cellular outputs to thermal inputs. Nat. Rev. Microbiol., 2012, 10(10), 693-704.
[14]
Kregel, K.C. Heat shock proteins: Modifying factors in physiological stress responses and acquired thermotolerance. J. Appl. Physiol., 2002, 92(5), 2177-2186.
[15]
Tiwari, S.; Thakur, R.; Shankar, J. Role of heat-shock proteins in cellular function and in the biology of fungi. Biotechnol. Res. Int., 2015, 2015, 132635.
[16]
Gong, Y.; Kakihara, Y.; Krogan, N.; Greenblatt, J.; Emili, A.; Zhang, Z.; Houry, W.A. An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: Implications to protein folding pathways in the cell. Mol. Syst. Biol., 2009, 5, 275.
[17]
Verghese, J.; Abrams, J.; Wang, Y.; Morano, K.A. Biology of the heat shock response and protein chaperones: Budding yeast (Saccharomyces cerevisiae) as a model system. Microbiol. Mol. Biol. Rev., 2012, 76(2), 115-158.
[18]
Lamoth, F.; Juvvadi, P.R.; Fortwendel, J.R.; Steinbach, W.J. Heat shock protein 90 is required for conidiation and cell wall integrity in Aspergillus fumigatus. Eukaryot. Cell, 2012, 11(11), 1324-1332.
[19]
Leach, M.D.; Budge, S.; Walker, L.; Munro, C.; Cowen, L.E.; Brown, A.J. Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast. PLoS Pathog., 2012, 8(12), e1003069.
[20]
Singh-Babak, S.D.; Babak, T.; Diezmann, S.; Hill, J.A.; Xie, J.L.; Chen, Y.L.; Poutanen, S.M.; Rennie, R.P.; Heitman, J.; Cowen, L.E. Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata. PLoS Pathog., 2012, 8(5), e1002718.
[21]
Juvvadi, P.R.; Lee, S.C.; Heitman, J.; Steinbach, W.J. Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach. Virulence, 2017, 8(2), 186-197.
[22]
Lamoth, F.; Juvvadi, P.R.; Steinbach, W.J. Heat shock protein 90 (Hsp90): A novel antifungal target against Aspergillus fumigatus. Crit. Rev. Microbiol., 2016, 42(2), 310-321.
[23]
Cowen, L.E. The fungal Achilles’ heel: Targeting Hsp90 to cripple fungal pathogens. Curr. Opin. Microbiol., 2013, 16(4), 377-384.
[24]
Bowman, S.M.; Free, S.J. The structure and synthesis of the fungal cell wall. BioEssays, 2006, 28(8), 799-808.
[25]
Gow, N.A.R.; Latge, J.P.; Munro, C.A. The fungal cell wall: Structure, biosynthesis, and function. Microbiol. Spectr., 2017, 5(3)
[http://dx.doi.org/10.1128/microbiolspec.FUNK-0035-2016]
[26]
Beauvais, A.; Latge, J.P. Membrane and cell wall targets in Aspergillus fumigatus. Drug Resist. Updat., 2001, 4(1), 38-49.
[27]
Erwig, L.P.; Gow, N.A. Interactions of fungal pathogens with phagocytes. Nat. Rev. Microbiol., 2016, 14(3), 163-176.
[28]
Levin, D.E. Regulation of cell wall biogenesis in Saccharomyces cerevisiae: The cell wall integrity signaling pathway. Genetics, 2011, 189(4), 1145-1175.
[29]
Robbins, N.; Wright, G.D.; Cowen, L.E. Antifungal drugs: The current armamentarium and development of new agents. Microbiol. Spectr., 2016, 4(5)
[http://dx.doi.org/10.1128/microbiolspec.FUNK-0002-2016]
[30]
Denning, D.W. Echinocandin antifungal drugs. Lancet, 2003, 362(9390), 1142-1151.
[31]
Chang, C.C.; Slavin, M.A.; Chen, S.C. New developments and directions in the clinical application of the echinocandins. Arch. Toxicol., 2017, 91(4), 1613-1621.
[32]
Feder, M.E.; Hofmann, G.E. Heat-shock proteins, molecular chaperones, and the stress response: Evolutionary and ecological physiology. Annu. Rev. Physiol., 1999, 61, 243-282.
[33]
Douglas, C.M. Fungal beta (1,3)-D-glucan synthesis. Med. Mycol., 2001, 39(Suppl. 1), 55-66.
[34]
Steinbach, W.J.; Lamoth, F.; Juvvadi, P.R. Potential microbiological effects of higher dosing of echinocandins. Clin. Infect. Dis., 2015, 61(Suppl. 6), S669-S677.
[35]
Fortwendel, J.R.; Juvvadi, P.R.; Pinchai, N.; Perfect, B.Z.; Alspaugh, J.A.; Perfect, J.R.; Steinbach, W.J. Differential effects of inhibiting chitin and 1,3-beta-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus. Antimicrob. Agents Chemother., 2009, 53(2), 476-482.
[36]
Stevens, D.A.; Ichinomiya, M.; Koshi, Y.; Horiuchi, H. Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for beta-1,6-glucan synthesis inhibition by caspofungin. Antimicrob. Agents Chemother., 2006, 50(9), 3160-3161.
[37]
Walsh, T.J.; Anaissie, E.J.; Denning, D.W.; Herbrecht, R.; Kontoyiannis, D.P.; Marr, K.A.; Morrison, V.A.; Segal, B.H.; Steinbach, W.J.; Stevens, D.A.; van Burik, J.A.; Wingard, J.R.; Patterson, T.F. Infectious diseases society of A., treatment of aspergillosis: Clinical practice guidelines of the infectious diseases society of America. Clin. Infect. Dis., 2008, 46(3), 327-360.
[38]
Dichtl, K.; Helmschrott, C.; Dirr, F.; Wagener, J. Deciphering cell wall integrity signalling in Aspergillus fumigatus: Identification and functional characterization of cell wall stress sensors and relevant Rho GTPases. Mol. Microbiol., 2012, 83(3), 506-519.
[39]
Rocha, M.C.; Fabri, J.H.; Franco de Godoy, K.; Alves de Castro, P.; Hori, J.I.; Ferreira da Cunha, A.; Arentshorst, M.; Ram, A.F.; van den Hondel, C.A.; Goldman, G.H.; Malavazi, I. Aspergillus fumigatus MADS-Box transcription factor rlmA is required for regulation of the cell wall integrity and virulence. G3 (Bethesda), 2016, 6(9), 2983-3002.
[40]
Rocha, M.C.; Godoy, K.F.; de Castro, P.A.; Hori, J.I.; Bom, V.L.; Brown, N.A.; Cunha, A.F.; Goldman, G.H.; Malavazi, I. The Aspergillus fumigatus pkcAG579R mutant is defective in the activation of the cell wall integrity pathway but is dispensable for virulence in a neutropenic mouse infection model. PLoS One, 2015, 10(8), e0135195.
[41]
Roman, E.; Alonso-Monge, R.; Miranda, A.; Pla, J. The Mkk2 MAPKK regulates cell wall biogenesis in cooperation with the Cek1-pathway in Candida albicans. PLoS One, 2015, 10(7), e0133476.
[42]
Roman, E.; Arana, D.M.; Nombela, C.; Alonso-Monge, R.; Pla, J. MAP kinase pathways as regulators of fungal virulence. Trends Microbiol., 2007, 15(4), 181-190.
[43]
Roman, E.; Correia, I.; Salazin, A.; Fradin, C.; Jouault, T.; Poulain, D.; Liu, F.T.; Pla, J. The Cek1mediated MAP kinase pathway regulates exposure of alpha1,2 and beta1,2mannosides in the cell wall of Candida albicans modulating immune recognition. Virulence, 2016, 7(5), 558-577.
[44]
Valiante, V.; Baldin, C.; Hortschansky, P.; Jain, R.; Thywissen, A.; Strassburger, M.; Shelest, E.; Heinekamp, T.; Brakhage, A.A. The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors. Mol. Microbiol., 2016, 102(2), 321-335.
[45]
Levin, D.E. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev., 2005, 69(2), 262-291.
[46]
Bruder-Nascimento, A.C.; Dos Reis, T.F.; de Castro, P.A.; Hori, J.I.; Bom, V.L.; de Assis, L.J.; Ramalho, L.N.; Rocha, M.C.; Malavazi, I.; Brown, N.A.; Valiante, V.; Brakhage, A.A.; Hagiwara, D.; Goldman, G.H. Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for Aspergillus fumigatus virulence. Mol. Microbiol., 2016, 100(5), 841-859.
[47]
Jain, R.; Valiante, V.; Remme, N.; Docimo, T.; Heinekamp, T.; Hertweck, C.; Gershenzon, J.; Haas, H.; Brakhage, A.A. The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus. Mol. Microbiol., 2011, 82(1), 39-53.
[48]
Valiante, V.; Jain, R.; Heinekamp, T.; Brakhage, A.A. The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus. Fungal Genet. Biol., 2009, 46(12), 909-918.
[49]
Valiante, V.; Macheleidt, J.; Foge, M.; Brakhage, A.A. The Aspergillus fumigatus cell wall integrity signaling pathway: Drug target, compensatory pathways, and virulence. Front. Microbiol., 2015, 6, 325.
[50]
Munro, C.A.; Selvaggini, S.; de Bruijn, I.; Walker, L.; Lenardon, M.D.; Gerssen, B.; Milne, S.; Brown, A.J.; Gow, N.A. The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol. Microbiol., 2007, 63(5), 1399-1413.
[51]
Herrmann, M.; Sprote, P.; Brakhage, A.A. Protein kinase C (PkcA) of Aspergillus nidulans is involved in penicillin production. Appl. Environ. Microbiol., 2006, 72(4), 2957-2970.
[52]
Gustin, M.C.; Albertyn, J.; Alexander, M.; Davenport, K. MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev., 1998, 62(4), 1264-1300.
[53]
Watanabe, Y.; Irie, K.; Matsumoto, K. Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol. Cell. Biol., 1995, 15(10), 5740-5749.
[54]
Watanabe, Y.; Takaesu, G.; Hagiwara, M.; Irie, K.; Matsumoto, K. Characterization of a serum response factor-like protein in Saccharomyces cerevisiae, Rlm1, which has transcriptional activity regulated by the Mpk1 (Slt2) mitogen-activated protein kinase pathway. Mol. Cell. Biol., 1997, 17(5), 2615-2623.
[55]
Jung, U.S.; Levin, D.E. Genome-wide analysis of gene expression regulated by the yeast cell wall integrity signalling pathway. Mol. Microbiol., 1999, 34(5), 1049-1057.
[56]
Dirr, F.; Echtenacher, B.; Heesemann, J.; Hoffmann, P.; Ebel, F.; Wagener, J. AfMkk2 is required for cell wall integrity signaling, adhesion, and full virulence of the human pathogen Aspergillus fumigatus. Int. J. Med. Microbiol., 2010, 300(7), 496-502.
[57]
Fujioka, T.; Mizutani, O.; Furukawa, K.; Sato, N.; Yoshimi, A.; Yamagata, Y.; Nakajima, T.; Abe, K. MpkA-Dependent and -independent cell wall integrity signaling in Aspergillus nidulans. Eukaryot. Cell, 2007, 6(8), 1497-1510.
[58]
Khatun, R.; Lakin-Thomas, P. Activation and localization of protein kinase C in Neurospora crassa. Fungal Genet. Biol., 2011, 48(4), 465-473.
[59]
LaFayette, S.L.; Collins, C.; Zaas, A.K.; Schell, W.A.; Betancourt-Quiroz, M.; Gunatilaka, A.A.; Perfect, J.R.; Cowen, L.E. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog., 2010, 6(8), e1001069.
[60]
Cowen, L.E.; Lindquist, S. Hsp90 potentiates the rapid evolution of new traits: Drug resistance in diverse fungi. Science, 2005, 309(5744), 2185-2189.
[61]
Lamoth, F.; Alexander, B.D.; Juvvadi, P.R.; Steinbach, W.J. Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species. J. Antimicrob. Chemother., 2015, 70(5), 1408-1411.
[62]
Verma, S.; Goyal, S.; Jamal, S.; Singh, A.; Grover, A. Hsp90: Friends, clients and natural foes. Biochimie, 2016, 127, 227-240.
[63]
Wayne, N.; Bolon, D.N. Dimerization of Hsp90 is required for in vivo function. Design and analysis of monomers and dimers. J. Biol. Chem., 2007, 282(48), 35386-35395.
[64]
Hawle, P.; Siepmann, M.; Harst, A.; Siderius, M.; Reusch, H.P.; Obermann, W.M. The middle domain of Hsp90 acts as a discriminator between different types of client proteins. Mol. Cell. Biol., 2006, 26(22), 8385-8395.
[65]
Dollins, D.E.; Warren, J.J.; Immormino, R.M.; Gewirth, D.T. Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones. Mol. Cell, 2007, 28(1), 41-56.
[66]
Lamoth, F.; Juvvadi, P.R.; Gehrke, C.; Asfaw, Y.G.; Steinbach, W.J. Transcriptional activation of heat shock protein 90 mediated via a proximal promoter region as trigger of caspofungin resistance in Aspergillus fumigatus. J. Infect. Dis., 2014, 209(3), 473-481.
[67]
Lamoth, F.; Juvvadi, P.R.; Soderblom, E.J.; Moseley, M.A.; Steinbach, W.J. Hsp70 and the cochaperone StiA (Hop) orchestrate Hsp90-Mediated caspofungin tolerance in Aspergillus fumigatus. Antimicrob. Agents Chemother., 2015, 59(8), 4727-4733.
[68]
Lee, C.T.; Graf, C.; Mayer, F.J.; Richter, S.M.; Mayer, M.P. Dynamics of the regulation of Hsp90 by the co-chaperone Sti1. EMBO J., 2012, 31(6), 1518-1528.
[69]
Li, J.; Soroka, J.; Buchner, J. The Hsp90 chaperone machinery: Conformational dynamics and regulation by co-chaperones. Biochim. Biophys. Acta, 2012, 1823(3), 624-635.
[70]
Mollapour, M.; Neckers, L. Post-translational modifications of Hsp90 and their contributions to chaperone regulation. Biochim. Biophys. Acta, 2012, 1823(3), 648-655.
[71]
Robbins, N.; Leach, M.D.; Cowen, L.E. Lysine deacetylases Hda1 and Rpd3 regulate Hsp90 function thereby governing fungal drug resistance. Cell Rep., 2012, 2(4), 878-888.
[72]
Cowen, L.E.; Carpenter, A.E.; Matangkasombut, O.; Fink, G.R.; Lindquist, S. Genetic architecture of Hsp90-dependent drug resistance. Eukaryot. Cell, 2006, 5(12), 2184-2188.
[73]
Lamoth, F.; Juvvadi, P.R.; Soderblom, E.J.; Moseley, M.A.; Asfaw, Y.G.; Steinbach, W.J. Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother., 2014, 58(4), 1889-1896.
[74]
Mollapour, M.; Tsutsumi, S.; Truman, A.W.; Xu, W.; Vaughan, C.K.; Beebe, K.; Konstantinova, A.; Vourganti, S.; Panaretou, B.; Piper, P.W.; Trepel, J.B.; Prodromou, C.; Pearl, L.H.; Neckers, L. Threonine 22 phosphorylation attenuates Hsp90 interaction with cochaperones and affects its chaperone activity. Mol. Cell, 2011, 41(6), 672-681.
[75]
Martinez-Ruiz, A.; Villanueva, L.; Gonzalez de Orduna, C.; Lopez-Ferrer, D.; Higueras, M.A.; Tarin, C.; Rodriguez-Crespo, I.; Vazquez, J.; Lamas, S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc. Natl. Acad. Sci. USA, 2005, 102(24), 8525-8530.
[76]
Retzlaff, M.; Stahl, M.; Eberl, H.C.; Lagleder, S.; Beck, J.; Kessler, H.; Buchner, J. Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep., 2009, 10(10), 1147-1153.
[77]
McClellan, A.J.; Xia, Y.; Deutschbauer, A.M.; Davis, R.W.; Gerstein, M.; Frydman, J. Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches. Cell, 2007, 131(1), 121-135.
[78]
Zhao, R.; Davey, M.; Hsu, Y.C.; Kaplanek, P.; Tong, A.; Parsons, A.B.; Krogan, N.; Cagney, G.; Mai, D.; Greenblatt, J.; Boone, C.; Emili, A.; Houry, W.A. Navigating the chaperone network: An integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell, 2005, 120(5), 715-727.
[79]
Altwasser, R.; Baldin, C.; Weber, J.; Guthke, R.; Kniemeyer, O.; Brakhage, A.A.; Linde, J.; Valiante, V. Network modeling reveals cross talk of MAP kinases during adaptation to caspofungin stress in Aspergillus fumigatus. PLoS One, 2015, 10(9), e0136932.
[80]
Diezmann, S.; Michaut, M.; Shapiro, R.S.; Bader, G.D.; Cowen, L.E. Mapping the Hsp90 genetic interaction network in Candida albicans reveals environmental contingency and rewired circuitry. PLoS Genet., 2012, 8(3), e1002562.
[81]
Malavazi, I.; Goldman, G.H.; Brown, N.A. The importance of connections between the cell wall integrity pathway and the unfolded protein response in filamentous fungi. Brief. Funct. Genomics, 2014, 13(6), 456-470.
[82]
Feng, X.; Krishnan, K.; Richie, D.L.; Aimanianda, V.; Hartl, L.; Grahl, N.; Powers-Fletcher, M.V.; Zhang, M.; Fuller, K.K.; Nierman, W.C.; Lu, L.J.; Latge, J.P.; Woollett, L.; Newman, S.L.; Cramer, R.A. Jr.; Rhodes, J.C.; Askew, D.S. HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS Pathog., 2011, 7(10), e1002330.
[83]
Richie, D.L.; Hartl, L.; Aimanianda, V.; Winters, M.S.; Fuller, K.K.; Miley, M.D.; White, S.; McCarthy, J.W.; Latge, J.P.; Feldmesser, M.; Rhodes, J.C.; Askew, D.S. A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS Pathog., 2009, 5(1), e1000258.
[84]
Rodriguez-Pena, J.M.; Garcia, R.; Nombela, C.; Arroyo, J. The High-Osmolarity Glycerol (HOG) and Cell Wall Integrity (CWI) signalling pathways interplay: A yeast dialogue between MAPK routes. Yeast, 2010, 27(8), 495-502.
[85]
Saito, H. Regulation of cross-talk in yeast MAPK signaling pathways. Curr. Opin. Microbiol., 2010, 13(6), 677-683.
[86]
Alonso-Monge, R.; Navarro-Garcia, F.; Molero, G.; Diez-Orejas, R.; Gustin, M.; Pla, J.; Sanchez, M.; Nombela, C. Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans. J. Bacteriol., 1999, 181(10), 3058-3068.
[87]
Bahn, Y.S.; Kojima, K.; Cox, G.M.; Heitman, J. Specialization of the HOG pathway and its impact on differentiation and virulence of Cryptococcus neoformans. Mol. Biol. Cell, 2005, 16(5), 2285-2300.
[88]
Hawle, P.; Horst, D.; Bebelman, J.P.; Yang, X.X.; Siderius, M.; van der Vies, S.M. CDC37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p). Eukaryot. Cell, 2007, 6(3), 521-532.
[89]
Steinbach, W.J.; Reedy, J.L.; Cramer, R.A.; Perfect, J.R.; Heitman, J. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat. Rev. Microbiol., 2007, 5(6), 418-430.
[90]
Juvvadi, P.R.; Lamoth, F.; Steinbach, W.J. Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis. Fungal Biol. Rev., 2014, 28(2-3), 56-69.
[91]
da Silva Ferreira, M.E.; Heinekamp, T.; Hartl, A.; Brakhage, A.A.; Semighini, C.P.; Harris, S.D.; Savoldi, M.; de Gouvea, P.F.; de Souza Goldman, M.H.; Goldman, G.H. Functional characterization of the Aspergillus fumigatus calcineurin. Fungal Genet. Biol., 2007, 44(3), 219-230.
[92]
Singh, S.D.; Robbins, N.; Zaas, A.K.; Schell, W.A.; Perfect, J.R.; Cowen, L.E. Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog., 2009, 5(7), e1000532.
[93]
Sanglard, D.; Ischer, F.; Marchetti, O.; Entenza, J.; Bille, J. Calcineurin A of Candida albicans: Involvement in antifungal tolerance, cell morphogenesis and virulence. Mol. Microbiol., 2003, 48(4), 959-976.
[94]
Steinbach, W.J.; Cramer, R.A. Jr.; Perfect, B.Z.; Asfaw, Y.G.; Sauer, T.C.; Najvar, L.K.; Kirkpatrick, W. R.; Patterson, T.F.; Benjamin, D.K.Jr.; Heitman, J.; Perfect, J.R. Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus. Eukaryot. Cell, 2006, 5(7), 1091-1103.
[95]
Cowen, L.E. The evolution of fungal drug resistance: Modulating the trajectory from genotype to phenotype. Nat. Rev. Microbiol., 2008, 6(3), 187-198.
[96]
O’Meara, T.R.; Veri, A.O.; Polvi, E.J.; Li, X.; Valaei, S.F.; Diezmann, S.; Cowen, L.E. Mapping the Hsp90 genetic network reveals ergosterol biosynthesis and phosphatidylinositol-4-kinase signaling as core circuitry governing cellular stress. PLoS Genet., 2016, 12(6), e1006142.
[97]
Shapiro, R.S.; Zaas, A.K.; Betancourt-Quiroz, M.; Perfect, J.R.; Cowen, L.E. The Hsp90 co-chaperone Sgt1 governs Candida albicans morphogenesis and drug resistance. PLoS One, 2012, 7(9), e44734.
[98]
Shapiro, R.S.; Sellam, A.; Tebbji, F.; Whiteway, M.; Nantel, A.; Cowen, L.E. Pho85, Pcl1, and Hms1 signaling governs Candida albicans morphogenesis induced by high temperature or Hsp90 compromise. Curr. Biol., 2012, 22(6), 461-470.
[99]
Jacob, T.R.; Peres, N.T.; Martins, M.P.; Lang, E.A.; Sanches, P.R.; Rossi, A.; Martinez-Rossi, N.M. Heat shock protein 90 (Hsp90) as a molecular target for the development of novel drugs against the dermatophyte Trichophyton rubrum. Front. Microbiol., 2015, 6, 1241.
[100]
Cordeiro Rde, A.; Evangelista, A.J.; Serpa, R.; Marques, F.J.; de Melo, C.V.; de Oliveira, J.S.; Franco Jda, S.; de Alencar, L.P.; Bandeira Tde, J.; Brilhante, R.S.; Sidrim, J.J.; Rocha, M.F. Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex. Microbiology, 2016, 162(2), 309-317.
[101]
Bui, D.C.; Lee, Y.; Lim, J.Y.; Fu, M.; Kim, J.C.; Choi, G.J.; Son, H.; Lee, Y.W. Heat shock protein 90 is required for sexual and asexual development, virulence, and heat shock response in Fusarium graminearum. Sci. Rep., 2016, 6, 28154.
[102]
Editorial: Stop neglecting fungi. Nat. Microbiol., 2017, 2, 17120.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy