 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 01, 2010 |
| Title |
Aspergillus fumigatus HapX-mediated iron starvation adaption is required for virulence. |
| Platform organism |
Aspergillus fumigatus Af293 |
| Sample organism |
Aspergillus fumigatus |
| Experiment type |
Expression profiling by array
|
| Summary |
Iron is an essential cofactor for a wide range of cellular processes. Previous studies have shown that siderophore-mediated uptake and intracellular handling of iron are crucial for virulence of Aspergillus fumigatus. Here we show that the bzip-type transcription factor HapX plays a crucial role in the transcriptional remodeling required for adaption to iron starvation in this opportunistic fungal pathogen. HapX was found to be interconnected in a negative feed-back loop with the previously identified iron regulator SreA: SreA repressed expression of hapX during iron sufficiency and HapX repressed sreA during iron starvation. Genome-wide transcriptional profiling and analysis of selected metabolites (protophorphyrine IX, siderophores and amino acids) indicated extensive metabolic remodeling in response to iron starvation. HapX was found to participate in both, repression and activation of genes during iron starvation. HapX was in particular required for repression of iron-dependent and mitochondrial-localized activities including respiration, TCA cycle, amino acid metabolism, iron-sulfur-cluster biosynthesis and heme biosynthesis. Pathways positively affected by HapX included production of siderophores and the ribotoxin and major allergen AspF1. Analysis of the free amino acid pool revealed HapX-dependent coordination of the production of siderophores with the supply of its precursor ornithine. Consistent with the hapX expression pattern, HapX-deficiency was deleterious with respect to growth rate and conidiation during iron depleted but not iron-replete conditions. HapX-deficiency caused significant attenuation of virulence in a murine model aspergillosis underlining that A. fumigatus faces iron starvation in the host and that the HapX-dependent metabolic reprogramming is therefore crucial for virulence.
|
| |
|
| Overall design |
A. fumigatus 293 and hapX mutants were grown in the presence and absence of iron and in cultures shifted from no iron to iron-containing conditions after 1 h incubation. Hybridizations were performed with biological replicates for wt vs hapX +/- iron. For the iron-shift experiments, there were biological replicates for wt in both conditions and for hapX in -iron but there was only a single biological sample for hapX iron-shift sample. All hybs were performed with flip-dye pairs.
|
| |
|
| Contributor(s) |
Varga JJ, Beckmann N, Gsalla F, Schrettl M, Heinekamp T, Jacobsen ID, Moussa TA, Wang S, Werner ER, Nierman WC, Brakhage AA, Haas H |
| Citation(s) |
20941352 |
| |
| Submission date |
May 28, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
John Varga |
| E-mail(s) |
j.varga@yahoo.com
|
| Organization name |
Emory University
|
| Department |
Pediatrics
|
| Lab |
Goldberg
|
| Street address |
1510 Clifton Road
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30324 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10341 |
JCVI Aspergillus fumigatus AF293 29.9K amplicon array |
|
| Samples (8)
|
| GSM548300 |
AF293 compared to hapX mutant in the presence of iron, replicate 1 |
| GSM548301 |
AF293 compared to hapX mutant in the presence of iron, replicate 2 |
| GSM548302 |
AF293 adaptation from iron- to iron+ conditions, replicate 1 |
| GSM548303 |
AF293 compared to hapX mutant in the absence of iron, replicate 1 |
| GSM548304 |
AF293 adaptation from iron- to iron+ conditions, replicate 2 |
| GSM548305 |
AF293 compared to hapX mutant in the absence of iron, replicate 2 |
| GSM548306 |
hapX adaptation from iron- to iron+ conditions, replicate 1 |
| GSM548307 |
hapX adaptation from iron- to iron+ conditions, replicate 2 |
|
| Relations |
| BioProject |
PRJNA128985 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22052_RAW.tar |
13.1 Mb |
(http)(custom) |
TAR (of MEV) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...