Table 5.
Singled out best targets from the combined pipeline regarding A. fumigatusa.
| Gene | Iron deficieny | In vivo | Hypoxia adapt. | Metabolic category | Evidence in literature | Genetic test worthwhile | Currently tested | Annotation |
|---|---|---|---|---|---|---|---|---|
| Sup6 | ||||||||
| AFUA_1G06940 | 0.000 | 0.820 | −1.855 | AA | 19 | Chorismate synthase (ARO2) | ||
| AFUA_3G04210 | 1.052 | −1.058 | −1.474 | FA | 1 | Fatty acid synthase alpha subunit FasA | ||
| AFUA_2G10520 | 0.000 | −0.757 | −3.258 | CAF | 2.3 | Urate oxydase UaZ | ||
| AFUA_2G06230 | 0.000 | −1.210 | 0.000 | AA | 4 | Glutamine amidotransferase:cyclase (HisH/F) | ||
| AFUA_3G04220 | 1.153 | −1.971 | 0.000 | FA | 1 | Fatty acid synthase beta subunit (FasB) | ||
| AFUA_3G09290 | −0.706 | −0.719 | 1.479 | AA | Phosphoglycerate mutase, 2,3-bisphosphoglycerate-independent | |||
| AFUA_6G04700 | 0.000 | −1.013 | 1.162 | AA;GLU | Imidazoleglycerol-phosphate dehydratase (HisB) | |||
| AFUA_3G06830 | 0.000 | −1.684 | 0.945 | AA;GLU | Aspartate-semialdehyde dehydrogenase (HOM2) | |||
| AFUA_1G14570 | 0.000 | 1.042 | −2.718 | AA_HIS | Phosphoribosyl-AMP cyclohydrolase (HIS4) | |||
| AFUA_5G06160 | 0.000 | NA | 0.000 | AA_HIS | 5-proFAR isomerase (HIS6) | |||
| AFUA_5G13130 | 0.000 | 0.037 | 0.000 | AA_a | 5 | 19 | Chorismate mutase (AroC) | |
| *AFUA_2G10740 | 0.000 | −1.164 | 0.000 | THI | Thiamin biosynthesis protein (Thi-4) | |||
| AFUA_4G06460 | 0.000 | 2.834 | 0.000 | AA_a | Pentafunctional AROM polypeptide (ARO1) | |||
| AFUA_3G14490 | 0.000 | −1.401 | −1.574 | AA | Ketol-acid reductoisomerase (ILV5) | |||
| AFUA_5G05590 | 0.000 | −1.060 | 1.703 | AA_s | Aspartokinase (HOM3) | |||
| AFUA_1G05530 | 0.000 | 0.147 | 0.000 | PYR | Uridine nucleosidase Urh1 | |||
| AFUA_5G05820 | 0.000 | −2.065 | 1.107 | AA_s | Homoserine kinase (THR1) | |||
| AFUA_4G04030 | 0.000 | NA | 0.000 | AA_HIS | Histidinol-phosphatase (HIS2) | |||
| AFUA_4G11980 | 0.000 | 0.083 | 0.000 | AA_a | Anthranilate phosphoribosyltransferase (TRP4) | |||
| *AFUA_6G12400 | 0.000 | −0.031 | −1.568 | GLU | 6 | 1,3-beta-glucan synthase catalytic subunit FksP | ||
| AFUA_4G13680 | 0.000 | −0.112 | 0.000 | AA_s | Phosphatidylserine synthase | |||
| Sup2 | ||||||||
| AFUA_6G11390 | −0.926 | 0.459 | −2.196 | 7 | 1,3-beta-glucanosyltransferase Gel2 | |||
| AFUA_5G01960 | −0.685 | −0.353 | −0.981 | 8 | Phosphate transporter (Pho88) | |||
| AFUA_1G09310 | 0.000 | 0.021 | 0.000 | DUF6 domain protein | ||||
| AFUA_3G11070 | 0.987 | −4.248 | 0.000 | GLU | Pyruvate decarboxylase PdcA | |||
| AFUA_5G08420 | −0.830 | −0.213 | 0.000 | MAPK | 9 | High osmolarity signaling protein Sho1 | ||
| AFUA_3G12800 | 0.000 | −0.645 | 0.000 | Clathrin-coated vesiclec protein (Bud7) | ||||
| *AFUA_2G10740 | 0.000 | −1.164 | 0.000 | THI | Thiamin biosynthesis protein (Thi-4) | |||
| AFUA_5G12190 | 0.000 | −4.310 | −0.817 | Transcription initiation factor subunit (TAF30) | ||||
| AFUA_4G09660 | 0.000 | 1.849 | 0.000 | Secretory component protein shr3 | ||||
| AFUA_2G12230 | 0.000 | −0.415 | 0.924 | Mitochondrial large ribosomal subunit protein L16 | ||||
| *AFUA_6G12400 | 0.000 | −0.031 | −1.568 | SUC | 6 | 1,3-beta-glucan synthase catalytic subunit FksP | ||
| AFUA_3G12320 | 0.000 | 0.506 | 0.837 | Lipase/serine esterase | ||||
| AFUA_1G06700 | 0.000 | −1.705 | 0.000 | 10 | Metacaspase CasA | |||
| AFUA_3G14140 | 0.367 | −1.273 | −1.262 | 10 | Metacaspase CasB | |||
| AFUA_4G13340 | 0.000 | −0.008 | −1.412 | DUF907 domain protein (FlcA) | ||||
| AFUA_2G17650 | −0.523 | 2.921 | −2.795 | DUF907 domain protein (FlcA) | ||||
| AFUA_2G17300 | 0.000 | 4.050 | 1.057 | GSH | Glutathione S-transferase | |||
| AFUA_1G17010 | 0.000 | 0.681 | 0.000 | GSH | Glutathione S-transferase | |||
| AFUA_2G09040 | 0.000 | 1.360 | 1.053 | vacuolar transporter chaperone (Vtc4) | ||||
| AFUA_2G04010 | 0.000 | −1.125 | 1.182 | SUC | 11 | Alpha, alpha-trehalose-phosphate synthase subunit (tpsA/B) | ||
| AFUA_6G12950 | 0.327 | −0.773 | 0.000 | SUC | 11 | Trehalose-phosphate synthase/phosphatase complex subunit Tps1 | ||
| ESSENTIAL GENES | ||||||||
| AFUA_3G14440 | 0.916 | −1.174 | 0.000 | Cytochrome c oxidase family protein | ||||
| AFUA_4G10480 | 0.000 | −2.375 | 1.812 | Mitochondrial large ribosomal subunit protein L30 | ||||
| FURTHER CONSIDERED TARGETS | ||||||||
| AFUA_2G15970 | 0.000 | −1.561 | 0.000 | PCS | Phosphatidylethanolamine N-methyltransferase | |||
| AFUA_5G05690 | 0.000 | 2.177 | 0.000 | AA | Prephenate dehydratase | |||
| AFUA_1G02110 | −0.832 | 0.086 | 0.000 | AA_a | 3-deoxy-7-phosphoheptulonate synthase | |||
| AFUA_7G04500 | 0.000 | 0.415 | 0.000 | AA_HIS | ATP phosphoribosyltransferase | |||
| AFUA_3G11640 | 0.000 | 0.914 | 0.986 | AA | Homoserine dehydrogenase | |||
| AFUA_4G10460 | 0.589 | −0.266 | 2.419 | AA | Homocitrate synthase | |||
| AFUA_5G07210 | 0.000 | −0.588 | 1.909 | AA | Homoserine O-acetyltransferase | |||
| AFUA_4G07360 | −0.622 | 0.052 | 0.000 | AA | Methionine synthase | |||
| AFUA_6G02860 | 0.000 | 1.827 | 1.566 | GLU | 12 | 2-methylisocitrate lyase | ||
| AFUA_6G03730 | −0.668 | 2.433 | 1.286 | AA | 2-methylcitrate hydrolyase | |||
| AFUA_1G09050 | 0.000 | −1.883 | 0.000 | PCS | 13 | Methylene-fatty-acyl-phospholipid synthase | ||
| AFUA_4G12990 | 0.000 | 1.271 | 0.000 | 14–16 | Thioredoxin reductase | |||
| AFUA_2G11290 | −0.452 | −0.573 | 0.000 | Orotate phosphoribosyltransferase 1 | ||||
| AFUA_4G12600 | 0.000 | −0.294 | 2.812 | Phosphoribosylaminoimidazole carboxylase | ||||
| AFUA_3G05650 | 0.000 | 0.474 | 1.158 | 17 | Trehalose-phosphatase | |||
| AFUA_7G01220 | 0.000 | −1.010 | 1.083 | Squalene synthase | ||||
| AFUA_5G10680 | 0.000 | −0.203 | 0.000 | Phosphomevalonate kinase | ||||
| AFUA_3G05730 | 0.000 | 0.024 | 0.000 | Nicotinate mononucleotide pyrophosphorylase | ||||
| AFUA_5G08120 | −0.402 | 3.931 | 1.030 | Glutamate N-acetyltransferase | ||||
| AFUA_2G10660 | −1.133 | −0.890 | 0.000 | 18 | Mannitol-1-phosphate 5-dehydrogenas | |||
| logFC: -3 |  |
3 | ||||||
Gene result in Sup10 + Sup14.
The heat map visualizes the logarithmic fold change in expression of respective genes. Green color depicts a negative regulation compared to control, red color a positive. White cells in the heatmap are considered to show significant (p > 0.05) expression changes. Yellow colors indicate new promising targets. Mutants currently tested by us and thus already available are shown by a blue box. Genes already successfully tested contain numbered literature references: (1) Edwards et al., 1998, (2) Oestreicher et al., 1993, (3) Oestreicher and Scazzocchio, 1993, (4) Valerius et al., 2001, (5) Krappmann et al., 1999, (6) Dichtl et al., 2015, (7) Mouyna et al., 2005, (8) de Gouvêa et al., 2008, (9) Ma et al., 2008, (10) Richie et al., 2007, (11) Al-Bader et al., 2010, (12) Brock, 2005, (13) Tao et al., 2010, (14) Schrettl et al., 2010, (15) Bruns et al., 2010, (16) Shi et al., 2012, (17) Puttikamonkul et al., 2010, (18) Ruijter et al., 2003, (19) Sasse et al., 2016. Pathway abbreviations: FA, fatty acid metabolism; AA, amino acid metabolism (aromats: AA_a; serin: AA_s; histidine: AA_HIS); SUC, sugar modifications; GSH, glutathione metabolism; THI, thiamin biosynthesis; GLU, gluconeogenesis.