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

References

• Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem. 1996;65:241–269.
   PubMed Web of Science ®Google Scholar
• Omer CA, Gibbs JB. Protein prenylation in eukaryotic microorganisms: genetics, biology and biochemistry. Mol Microbiol. 1994;11:219–225.
   PubMed Web of Science ®Google Scholar
• Wang M, Casey PJ. Protein prenylation: unique fats make their mark on biology. Nat Rev Mol Cell Biol. 2016;17:110–122.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Seabra MC, Reiss Y, Casey PJ, et al. Protein farnesyltransferase and geranylgeranyltransferase share a common α subunit. Cell. 1991;65:429–434.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Moores SL, Schaber MD, Mosser SD, et al. Sequence dependence of protein isoprenylation. J Biol Chem. 1991;266:14603–14610.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Casey PJ, Seabra MC. Protein Prenyltransferases. J Biol Chem. 1996;271:5289–5292.
   PubMed Web of Science ®Google Scholar
• Schafer WR, Rine J. Protein prenylation: genes, enzymes, targets, and functions. Annu Rev Genet. 1992;26:209–237.
   PubMed Web of Science ®Google Scholar
• Fortwendel JR. Ras-mediated signal transduction and virulence in human pathogenic fungi. Fungal genomics Biol. 2012;2:105.
   PubMedGoogle Scholar
• Harris SD. Cdc42/Rho GTPases in fungi: variations on a common theme. Mol Microbiol. 2011;79:1123–1127.
   PubMed Web of Science ®Google Scholar
• Philips M, Cox A. Geranylgeranyltransferase I as a target for anti-cancer drugs. J Clin Invest. 2007;117:1223–1225.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Alspaugh JA. Targeting protein localization for anti-infective therapy. Virulence. 2017;8:1105–1107.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Palsuledesai CC, Distefano MD. Protein prenylation: enzymes, therapeutics, and biotechnology applications. ACS Chem Biol. 2015;10:51–62.
   PubMed Web of Science ®Google Scholar
• Ochocki JD, Distefano MD. Prenyltransferase Inhibitors: treating human ailments from cancer to parasitic infections. Medchemcomm. 2013;4:476–492.
   PubMed Web of Science ®Google Scholar
• Song JL, White TC. RAM2: an essential gene in the prenylation pathway of Candida albicans. Microbiology. 2003;149:249–259.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Yelton MM, Hamer JE, Timberlake WE. Transformation of Aspergillus nidulans by using a trpC plasmid. Genetics. 1984;81:1470–1474.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Bhabhra R, Askew DS. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol. 2005;43(Suppl 1):S87–93.
   PubMedGoogle Scholar
• Albrecht D, Guthke R, Brakhage AA, et al. Integrative analysis of the heat shock response in Aspergillus fumigatus. BMC Genomics. 2010;11:32.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Chang YC, Tsai HF, Karos M, et al. THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet Biol. 2004;41:888–896.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Si H, Rittenour WR, Harris SD. Roles of Aspergillus nidulans Cdc42/Rho GTPase regulators in hyphal morphogenesis and development. Mycologia. 2016;108:543–555.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   Web of Science ®Google Scholar
• Beauvais A, Bruneau JM, Mol PC, et al. Glucan synthase complex of Aspergillus fumigatus. J Bacteriol. 2001;183:2273–2279.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Qiao J, Sun Y, Gao L, et al. Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp. Med Mycol. 2018;56:452–457.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar