title: Transcriptional and proteomic analysis of the Aspergillus fumigatus ΔprtT protease-deficient mutant.
abstract: Aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. The fungus invades the lungs and other organs, causing severe damage. Penetration of the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases to degrade the host structural barriers. The A. fumigatus transcription factor PrtT controls the expression of multiple secreted proteases. PrtT shows similarity to the fungal Gal4-type Zn(2)-Cys(6) DNA-binding domain of several transcription factors. In this work, we further investigate the function of this transcription factor by performing a transcriptional and a proteomic analysis of the ΔprtT mutant. Unexpectedly, microarray analysis revealed that in addition to the expected decrease in protease expression, expression of genes involved in iron uptake and ergosterol synthesis was dramatically decreased in the ΔprtT mutant. A second finding of interest is that deletion of prtT resulted in the upregulation of four secondary metabolite clusters, including genes for the biosynthesis of toxic pseurotin A. Proteomic analysis identified reduced levels of three secreted proteases (ALP1 protease, TppA, AFUA_2G01250) and increased levels of three secreted polysaccharide-degrading enzymes in the ΔprtT mutant possibly in response to its inability to derive sufficient nourishment from protein breakdown. This report highlights the complexity of gene regulation by PrtT, and suggests a potential novel link between the regulation of protease secretion and the control of iron uptake, ergosterol biosynthesis and secondary metabolite production in A. fumigatus.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine Ramat-Aviv, Tel-Aviv, Israel.
authors.forename: Shelly
authors.initials: S
authors.lastname: Hagag
authors.forename: Paula
authors.initials: P
authors.lastname: Kubitschek-Barreira
authors.forename: Gabriela W P
authors.initials: GW
authors.lastname: Neves
authors.forename: David
authors.initials: D
authors.lastname: Amar
authors.forename: William
authors.initials: W
authors.lastname: Nierman
authors.forename: Itamar
authors.initials: I
authors.lastname: Shalit
authors.forename: Ron
authors.initials: R
authors.lastname: Shamir
authors.forename: Leila
authors.initials: L
authors.lastname: Lopes-Bezerra
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D005656:Fungal Proteins; D010447:Peptide Hydrolases