Mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for Aspergillus fumigatus virulence

Virulence

Volumn 7, Issue 1, 2016, Pages 56-62

  Sasse, Anna ^a   Hamer, Stefanie N ^a,b   Amich, Jorge ^c   Binder, Jasmin ^d   Krappmann, Sven ^a,d  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^d UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Aspergillosis; Conditional promoter replacement; Glyphosate; Primary metabolism; Shikimate pathway; Tet ON

Indexed keywords

AMINO ACID; ANTIFUNGAL AGENT; AROMATIC AMINO ACID; GLYCINE; GLYPHOSATE;

AMINO ACID SYNTHESIS; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASPERGILLUS FUMIGATUS; CELL PROLIFERATION; CONTROLLED STUDY; FEMALE; FUNGAL COLONIZATION; FUNGAL METABOLISM; FUNGAL STRAIN; FUNGAL VIRULENCE; FUNGUS GROWTH; GENE EXPRESSION; GENE MUTATION; GENE REPRESSION; MOLECULAR CLONING; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; ANALOGS AND DERIVATIVES; ANIMAL; ASPERGILLOSIS; BAGG ALBINO MOUSE; BIOSYNTHESIS; CHEMISTRY; DISEASE MODEL; DRUG EFFECTS; GENETICS; HOST PATHOGEN INTERACTION; METABOLISM; MICROBIOLOGY; MUTATION; PATHOGENICITY; PHYSIOLOGY; VIRULENCE;

AMINO ACIDS, AROMATIC; ANIMALS; ANTIFUNGAL AGENTS; ASPERGILLOSIS; ASPERGILLUS FUMIGATUS; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; FEMALE; GLYCINE; HOST-PATHOGEN INTERACTIONS; MICE; MICE, INBRED BALB C; MUTATION; VIRULENCE;

EID: 84964031076     PISSN: 21505594     EISSN: 21505608     Source Type: Journal    
DOI: 10.1080/21505594.2015.1109766     Document Type: Article

References (32)

1. Rohmer L, Hocquet D, Miller SI. Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis. Trends Microbiol 2011; 19:341-8 http://dx.doi.org/10.1016/j.tim.2011.04.003
2. Andersen MR. Elucidation of primary metabolic pathways in Aspergillus species: Orphaned research in characterizing orphan genes. Brief Funct Genomics 2014; 13(6):451-5
3. Tekaia F, Latge JP. Aspergillus fumigatus: saprophyte or pathogen? Curr Opin Microbiol 2005; 8:385-92 http://dx.doi.org/10.1016/j.mib.2005.06.017
4. Rhodes JC. Aspergillus fumigatus: growth and virulence. Med Mycol 2006; 44 Suppl 1:S77-81 http://dx.doi.org/10.1080/13693780600779419
5. d’Enfert C, Diaquin M, Delit A, Wuscher N, Debeaupuis JP, Huerre M, Latge JP. Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus. Infect Immun 1996; 64:4401-5
6. Brown JS, Aufauvre-Brown A, Brown J, Jennings JM, Arst H, Jr., Holden DW. Signature-tagged and directed mutagenesis identify PABA synthetase as essential for Aspergillus fumigatus pathogenicity. Mol Microbiol 2000; 36:1371-80 http://dx.doi.org/10.1046/j.1365-2958.2000.01953.x
7. Liebmann B, Mühleisen TW, Müller M, Hecht M, Weidner G, Braun A, Brock M, Brakhage AA. Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose mouse infection model of invasive aspergillosis. Arch Microbiol 2004; 181:378-83 http://dx.doi.org/10.1007/s00203-004-0667-3
8. Schöbel F, Jacobsen ID, Brock M. Evaluation of lysine biosynthesis as an antifungal drug target: biochemical characterization of Aspergillus fumigatus homocitrate synthase and virulence studies. Eukaryot Cell 2010; 9:878-93 http://dx.doi.org/10.1128/EC.00020-10
9. Oliver JD, Kaye SJ, Tuckwell D, Johns AE, Macdonald DA, Livermore J, Warn PA, Birch M, Bromley MJ. The Aspergillus fumigatus dihydroxyacid dehydratase Ilv3A/IlvC is required for full virulence. PLoS One 2012; 7:e43559 http://dx.doi.org/10.1371/journal.pone.0043559
10. Gibson F. The elusive branch-point compound of aromatic amino acid biosynthesis. Trends Biochem Sci 1999; 24:36-8 http://dx.doi.org/10.1016/S0968-0004(98)01330-9
11. Herrmann KM, Weaver LM. The shikimate pathway. Annu Rev Plant Physiol Plant Mol Biol 1999; 50:473-503 http://dx.doi.org/10.1146/annurev.arplant.50.1.473
12. Bentley R. The shikimate pathway-a metabolic tree with many branches. Crit Rev Biochem Mol Biol 1990; 25:307-84 http://dx.doi.org/10.3109/10409239009090615
13. Roberts F, Roberts CW, Johnson JJ, Kyle DE, Krell T, Coggins JR, Coombs GH, Milhous WK, Tzipori S, Ferguson DJ, et al. Evidence for the shikimate pathway in apicomplexan parasites. Nature 1998; 393:801-5 http://dx.doi.org/10.1038/30718
14. Krappmann S, Bignell EM, Reichard U, Rogers T, Haynes K, Braus GH. The Aspergillus fumigatus transcriptional activator CpcA contributes significantly to the virulence of this fungal pathogen. Mol Microbiol 2004; 52:785-99 http://dx.doi.org/10.1111/j.1365-2958.2004.04015.x
15. Krappmann S, Helmstaedt K, Gerstberger T, Eckert S, Hoffmann B, Hoppert M, Schnappauf G, Braus GH. The aroC gene of Aspergillus nidulans codes for a monofunctional, allosterically regulated chorismate mutase. J Biol Chem 1999; 274:22275-82 http://dx.doi.org/10.1074/jbc.274.32.22275
16. Charles IG, Keyte JW, Brammar WJ, Smith M, Hawkins AR. The isolation and nucleotide sequence of the complex AROM locus of Aspergillus nidulans. Nucleic Acids Res 1986; 14:2201-13 http://dx.doi.org/10.1093/nar/14.5.2201
17. Osmani AH, Oakley BR, Osmani SA. Identification and analysis of essential Aspergillus nidulans genes using the heterokaryon rescue technique. Nat Protoc 2006; 1:2517-26 http://dx.doi.org/10.1038/nprot.2006.406
18. Hu W, Sillaots S, Lemieux S, Davison J, Kauffman S, Breton A, Linteau A, Xin C, Bowman J, Becker J, et al. Essential gene identification and drug target prioritization in Aspergillus fumigatus. PLoS Pathog 2007; 3:e24 http://dx.doi.org/10.1371/journal.ppat.0030024
19. Romero B, Turner G, Olivas I, Laborda F, De Lucas JR. The Aspergillus nidulans alcA promoter drives tightly regulated conditional gene expression in Aspergillus fumigatus permitting validation of essential genes in this human pathogen. Fungal Genet Biol 2003; 40:103-14 http://dx.doi.org/10.1016/S1087-1845(03)00090-2
20. 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; 83:506-19 http://dx.doi.org/10.1111/j.1365-2958.2011.07946.x
21. Helmschrott C, Sasse A, Samantaray S, Krappmann S, Wagener J. Upgrading fungal gene expression on demand: improved systems for doxycycline-dependent silencing in Aspergillus fumigatus. Appl Environ Microbiol 2013; 79:1751 http://dx.doi.org/10.1128/AEM.03626-12
22. Amich J, Krappmann S. Deciphering metabolic traits of the fungal pathogen Aspergillus fumigatus: redundancy vs. essentiality. Front Microbiol 2012; 3:414
23. Romero RM, Roberts MF, Phillipson JD. Chorismate mutase in microorganisms and plants. Phytochemistry 1995; 40:1015-25; http://dx.doi.org/10.1016/0031-9422(95)00408-Y
24. Romero RM, Roberts MF, Phillipson JD. Anthranilate synthase in microorganisms and plants. Phytochemistry 1995; 39:263-76 http://dx.doi.org/10.1016/0031-9422(95)00010-5
25. Sträter N, Schnappauf G, Braus G, Lipscomb WN. Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures. Structure 1997; 5:1437-52; http://dx.doi.org/10.1016/S0969-2126(97)00294-3
26. Lu Y, Deng J, Rhodes JC, Lu H, Lu LJ. Predicting essential genes for identifying potential drug targets in Aspergillus fumigatus. Comput Biol Chem 2014; 50:29-40 http://dx.doi.org/10.1016/j.compbiolchem.2014.01.011
27. Firon A, Beauvais A, Latge JP, Couve E, Grosjean-Cournoyer MC, d’Enfert C. Characterization of essential genes by parasexual genetics in the human fungal pathogen Aspergillus fumigatus: impact of genomic rearrangements associated with electroporation of DNA. Genetics 2002; 161:1077-87
28. Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, et al. Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol Microbiol 2003; 50:167-81 http://dx.doi.org/10.1046/j.1365-2958.2003.03697.x
29. Vogt K, Bhabhra R, Rhodes JC, Askew DS. Doxycycline-regulated gene expression in the opportunistic fungal pathogen Aspergillus fumigatus. BMC Microbiol 2005; 5:1 http://dx.doi.org/10.1186/1471-2180-5-1
30. Krappmann S, Sasse C, Braus GH. Gene targeting in Aspergillus fumigatus by homologous recombination is facilitated in a nonhomologous end joining-deficient genetic background. Eukaryot Cell 2006; 5:212-5 http://dx.doi.org/10.1128/EC.5.1.212-215.2006
31. Krappmann S, Bayram € O, Braus GH. Deletion and allelic exchange of the Aspergillus fumigatus veA locus via a novel recyclable marker module. Eukaryot Cell 2005; 4:1298-307 http://dx.doi.org/10.1128/EC.4.7.1298-1307.2005
32. Amich J, Schafferer L, Haas H, Krappmann S. Regulation of sulphur assimilation is essential for virulence and affects iron homeostasis of the human-pathogenic mould Aspergillus fumigatus. PLoS Pathog 2013; 9: e1003573 http://dx.doi.org/10.1371/journal.ppat.1003573