1,468
Views
5
CrossRef citations to date
0
Altmetric
Research Paper

Differential requirements of protein geranylgeranylation for the virulence of human pathogenic fungi

, , , ORCID Icon, , , , , & show all
Pages 511-526 | Received 14 Jan 2019, Accepted 10 May 2019, Published online: 25 May 2019

References

  • Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem. 1996;65:241–269.
  • Omer CA, Gibbs JB. Protein prenylation in eukaryotic microorganisms: genetics, biology and biochemistry. Mol Microbiol. 1994;11:219–225.
  • Wang M, Casey PJ. Protein prenylation: unique fats make their mark on biology. Nat Rev Mol Cell Biol. 2016;17:110–122.
  • Blanden MJ, Suazo KF, Hildebrandt ER, et al. Efficient farnesylation of an extended C-terminal C(x)3X sequence motif expands the scope of the prenylated proteome. J Biol Chem. 2018;293:2770–2785.
  • Seabra MC, Reiss Y, Casey PJ, et al. Protein farnesyltransferase and geranylgeranyltransferase share a common α subunit. Cell. 1991;65:429–434.
  • Mabanglo MF, Hast MA, Lubock NB, et al. Crystal structures of the fungal pathogen Aspergillus fumigatus protein farnesyltransferase complexed with substrates and inhibitors reveal features for antifungal drug design. Protein Sci. 2014;23:289–301.
  • Scott Reid T, Terry KL, Casey PJ, et al. Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol. 2004;343:417–433.
  • Moores SL, Schaber MD, Mosser SD, et al. Sequence dependence of protein isoprenylation. J Biol Chem. 1991;266:14603–14610.
  • Trueblood CE, Ohya Y, Rine J. Genetic evidence for in vivo cross-specificity of the CaaX-box protein prenyltransferases farnesyltransferase and geranylgeranyltransferase-I in Saccharomyces cerevisiae. Mol Cell Biol. 1993;13:4260–4275.
  • Casey PJ, Seabra MC. Protein Prenyltransferases. J Biol Chem. 1996;271:5289–5292.
  • Schafer WR, Rine J. Protein prenylation: genes, enzymes, targets, and functions. Annu Rev Genet. 1992;26:209–237.
  • Fortwendel JR. Ras-mediated signal transduction and virulence in human pathogenic fungi. Fungal genomics Biol. 2012;2:105.
  • Harris SD. Cdc42/Rho GTPases in fungi: variations on a common theme. Mol Microbiol. 2011;79:1123–1127.
  • Philips M, Cox A. Geranylgeranyltransferase I as a target for anti-cancer drugs. J Clin Invest. 2007;117:1223–1225.
  • Xu N, Shen N, Wang XX, et al. Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation. Sci China Life Sci. 2015;58:328–335.
  • Shen M, Pan P, Li Y, et al. Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling. Drug Discov Today. 2015;20:267–276.
  • Alspaugh JA. Targeting protein localization for anti-infective therapy. Virulence. 2017;8:1105–1107.
  • Qiao J, Gao P, Jiang X, et al. In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida. Ann Clin Microbiol Antimicrob. 2013;12:37.
  • Palsuledesai CC, Distefano MD. Protein prenylation: enzymes, therapeutics, and biotechnology applications. ACS Chem Biol. 2015;10:51–62.
  • Ochocki JD, Distefano MD. Prenyltransferase Inhibitors: treating human ailments from cancer to parasitic infections. Medchemcomm. 2013;4:476–492.
  • Song JL, White TC. RAM2: an essential gene in the prenylation pathway of Candida albicans. Microbiology. 2003;149:249–259.
  • McGeady P, Logan DA, Wansley DL. A protein-farnesyl transferase inhibitor interferes with the serum-induced conversion of Candida albicans from a cellular yeast form to a filamentous form. FEMS Microbiol Lett. 2002;213:41–44.
  • Vallim MA, Fernandes L, Alspaugh JA. The RAM1 gene encoding a protein-farnesyltransferase beta-subunit homologue is essential in Cryptococcus neoformans. Microbiology. 2004;150:1925–1935.
  • Hast MA, Nichols CB, Armstrong SM, et al. Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens. J Biol Chem. 2011;286:35149–35162.
  • Hast MA, Beese LS. Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate. J Biol Chem. 2008;283:31933–31940.
  • He B, Chen P, Chen SY, et al. RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins. Proc Natl Acad Sci U S A. 1991;88:11373–11377.
  • Nakayama H, Ueno K, Uno J, et al. Growth defects resulting from inhibiting ERG20 and RAM2 in Candida glabrata. FEMS Microbiol Lett. 2011;317:27–33.
  • Esher SK, Ost KS, Kozubowski L, et al. Relative contributions of prenylation and postprenylation processing in Cryptococcus neoformans pathogenesis. Mol Biol Physiol. 2016;1:1–18.
  • Yang W, Urano J, Tamanoi F. Protein farnesylation is critical for maintaining normal cell morphology and canavanine resistance in Schizosaccharomyces pombe. J Biol Chem. 2000;275:429–438.
  • Goodman LE, Judd SR, Farnsworth CC, et al. Mutants of Saccharomyces cerevisiae defective in the farnesylation of Ras proteins. Proc Natl Acad Sci U S A. 1990;87:9665–9669.
  • Kelly R, Card D, Register E, et al. Geranylgeranyltransferase I of Candida albicans: null mutants or enzyme inhibitors produce unexpected phenotypes. J Bacteriol. 2000;182:704–713.
  • Selvig K, Ballou ER, Nichols CB, et al. Restricted substrate specificity for the geranylgeranyltransferase-i enzyme in Cryptococcus neoformans: implications for virulence. Eukaryot Cell. 2013;12:1462–1471.
  • Norton TS, Al Abdallah Q, Hill AM, et al. The Aspergillus fumigatus farnesyltransferase β-subunit, RamA, mediates growth, virulence, and antifungal susceptibility. Virulence. 2017;8:1401–1416.
  • Yelton MM, Hamer JE, Timberlake WE. Transformation of Aspergillus nidulans by using a trpC plasmid. Genetics. 1984;81:1470–1474.
  • Da Silva Ferreira ME, Kress MRVZ, 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;5:207–211.
  • Al Abdallah Q, Martin-Vicente A, Souza ACO, et al. C-terminus proteolysis and palmitoylation cooperate for optimal plasma membrane localization of RasA in Aspergillus fumigatus. Front Microbiol. 2018;9:562.
  • Calvo AM, Bok J, Brooks W, et al. veA is required for toxin and sclerotial production in Aspergillus parasiticus. Appl Environ Microbiol. 2004;70:4733–4739.
  • Al Abdallah Q, Ge W, Fortwendel JR. A simple and universal system for gene manipulation in Aspergillus fumigatus: in vitro-assembled Cas9-guide RNA ribonucleoproteins coupled with microhomology repair templates. mSphere. 2017;2:e00446–17.
  • Helmschrott C, Sasse A, Samantaray S, et al. Upgrading fungal gene expression on demand: improved systems for doxycycline-dependent silencing in Aspergillus fumigatus. Appl Environ Microbiol. 2013;79:1751–1754.
  • Roemer T, Jiang B, Davison J, et al. Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol. 2003;50:167–181.
  • Fortwendel JR, Juvvadi PR, Pinchai N, et al. Differential effects of inhibiting chitin and 1,3-{beta}-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus. Antimicrob Agents Chemother. 2009;53:476–482.
  • CLSI. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard - second edition. CLSI document M38-A2. Wayne (PA): Clinical and Laboratory Standards Institute; 2008.
  • Koenig S, Rühmann B, Sieber V, et al. Quantitative assay of β-(1,3)–β-(1,6)–glucans from fermentation broth using aniline blue. Carbohydr Polym. 2017;174:57–64.
  • Bhabhra R, Askew DS. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol. 2005;43(Suppl 1):S87–93.
  • Albrecht D, Guthke R, Brakhage AA, et al. Integrative analysis of the heat shock response in Aspergillus fumigatus. BMC Genomics. 2010;11:32.
  • Alspaugh JA, Cavallo LM, Perfect JR, et al. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol Microbiol. 2000;36:352–365.
  • Dichtl K, Helmschrott C, Dirr F, et al. Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases. Mol Microbiol. 2012;83:506–519.
  • Bhabhra R, Miley MD, Mylonakis E, et al. Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect Immun. 2004;72:4731–4740.
  • Chang YC, Tsai HF, Karos M, et al. THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet Biol. 2004;41:888–896.
  • Adams AEM, Johnson DI, Longnecker RM, et al. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. J Cell Biol. 1990;111:131–142.
  • Johnson DI, Pringle JR. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol. 1990;111:143–152.
  • Ushinsky SC, Harcus D, Ash J, et al. CDC42 is required for polarized growth in human pathogen Candida albicans. Eukaryot Cell. 2002;1:95–104.
  • Ballou ER, Nichols CB, Miglia KJ, et al. Two CDC42 paralogues modulate Cryptococcus neoformans thermotolerance and morphogenesis under host physiological conditions. Mol Microbiol. 2010;75:763–780.
  • Kwon MJ, Arentshorst M, Roos ED, et al. Functional characterization of Rho GTPases in Aspergillus niger uncovers conserved and diverged roles of Rho proteins within filamentous fungi. Mol Microbiol. 2011;79:1151–1167.
  • Virag A, Lee MP, Si H, et al. Regulation of hyphal morphogenesis by cdc42 and rac1 homologues in Aspergillus nidulans. Mol Microbiol. 2007;66:1579–1596.
  • Si H, Rittenour WR, Harris SD. Roles of Aspergillus nidulans Cdc42/Rho GTPase regulators in hyphal morphogenesis and development. Mycologia. 2016;108:543–555.
  • Li H, Barker BM, Grahl N, et al. The small GTPase RacA mediates intracellular reactive oxygen species production, polarized growth, and virulence in the human fungal pathogen Aspergillus fumigatus. Eukaryot Cell. 2011;10:174–186.
  • Chi MH, Craven KD. RacA-mediated ROS signaling is required for polarized cell differentiation in conidiogenesis of Aspergillus fumigatus. PLoS One. 2016;11:1–13.
  • Beauvais A, Bruneau JM, Mol PC, et al. Glucan synthase complex of Aspergillus fumigatus. J Bacteriol. 2001;183:2273–2279.
  • Dichtl K, Samantaray S, Aimanianda V, et al. Aspergillus fumigatus devoid of cell wall β-1,3-glucan is viable, massively sheds galactomannan and is killed by septum formation inhibitors. Mol Microbiol. 2015;95:458–471.
  • Inoue SB, Qadota H, Arisawa M, et al. Prenylation of Rho1p is required for activation of yeast 1, 3-beta-glucan synthase. J Biol Chem. 1999;274:38119–38124.
  • Qiao J, Sun Y, Gao L, et al. Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp. Med Mycol. 2018;56:452–457.
  • Valiante V, Macheleidt J, Föge M, et al. The Aspergillus fumigatus cell wall integrity signalling pathway: drug target, compensatory pathways and virulence. Front Microbiol. 2015;6:1–12.