Project description:In lung diseases caused by the major mould pathogen Aspergillus fumigatus the pulmonary epithelium is destroyed by invasive growth of fungal hyphae, a process thought to require fungal proteases. Here we show that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In addition, A. fumigatus M-NM-^TpacC mutants aberrantly remodel the fungal cell wall during infection. This study defines distinct PacC-mediated mechanisms of host damage during pulmonary aspergillosis. ch1: treatment protocol Temporal transcriptional profiling of ATCC46645 strain and isogenic M-NM-^TpacC Aspergillus fumigatus mutant during murine infection
Project description:Aspergillus fumigatus mutant strains were collected from bronchoalveolar lavage fluids (BALFs) during acute mouse infection (4 and 12 hours).
Project description:Genomic DNA from five strains, Aspergillus fumigatus Af71, Aspergillus fumigatus Af294, Aspergillus clavatus, Neosartorya fenneliae, and Neosartorya fischeri, were co-hybridized with that of Aspergillus fumigatus Af293 and compared.
Project description:Iron restriction imposed by mammalian hosts during an infection is a common mechanism of defense to reduce or avoid the pathogen infection. Iron is essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis (IA), a disease that typically manifests in immunocompromised patients. A. fumigatus has two high affinity mechanisms of iron acquisition during infection: reductive iron assimilation (RIA) and siderophore-mediated iron uptake. It has been shown that siderophore production is important for A. fumigatus virulence, differently to the reductive iron uptake system. A. fumigatus PpzA, the catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as associated with iron assimilation. Transcriptomic and proteomic comparisons between ∆ppzA and wild-type strains under iron starvation showed that PpzA has a broad influence on genes involved in secondary metabolism. LC-MS under standard and iron starvation conditions confirmed that the ΔppzA mutant had reduced production of pyripyropene A (PPA), fumagillin, fumiquinazoline A, TAFC, and helvolic acid. The ΔppzA was shown to be avirulent in a neutropenic murine model of invasive pulmonary aspergillosis. PpzA plays an important role at the interface between iron starvation, regulation of SM production and pathogenicity in A. fumigatus.
Project description:Aspergillus fumigatus mutant strains were collected from bronchoalveolar lavage fluids (BALFs) during acute mouse infection (4 and 12 hours). Transcriptional analysis were conducted by comparison of each mutant with the wild type strain (CEA17) in a dye swap experiment. Besides, we performed the transcriptional profile of akuB(KU80) mutant compared to CEA17 wild type strain. All the strains were recovered from bronchoalveolar lavage fluid from CD1 mice infected with 10e8 spores for 4 and 12 hours.
Project description:Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections including invasive aspergillosis. We aimed to understand molecular targets of AMB in Aspergillus fumigatus (Afu) by genomic approaches. Keywords: Aspergillus fumigatus treated with amphotericin B for 24 hours
Project description:We report gene expression differences in Aspergillus fumigatus wild type, hrmA mutant, and overexpression under hypoxia and normoxia conditions
Project description:RNA expression of 773 host response genes following Aspergillus fumigatus infection in healthy neutrophils in the presence and absence of ibrutinib and/or TNFalpha
