scholarly journals Regulation of Sulphur Assimilation Is Essential for Virulence and Affects Iron Homeostasis of the Human-Pathogenic Mould Aspergillus fumigatus

2013 ◽  
Vol 9 (8) ◽  
pp. e1003573 ◽  
Author(s):  
Jorge Amich ◽  
Lukas Schafferer ◽  
Hubertus Haas ◽  
Sven Krappmann
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Homeostasis ◽  
Sulphur Assimilation

scholarly journals Regulatory interactions for iron homeostasis in Aspergillus fumigatus inferred by a Systems Biology approach

2012 ◽  
Vol 6 (1) ◽  
pp. 6 ◽  
Author(s):  
Jörg Linde ◽  
Peter Hortschansky ◽  
Eugen Fazius ◽  
Axel A Brakhage ◽  
Reinhard Guthke ◽  
...  
Keyword(s):  
Systems Biology ◽  
Aspergillus Fumigatus ◽  
Iron Homeostasis ◽  
Regulatory Interactions

scholarly journals Fungal iron homeostasis with a focus on Aspergillus fumigatus

2021 ◽  
Vol 1868 (1) ◽  
pp. 118885
Author(s):  
Matthias Misslinger ◽  
Peter Hortschansky ◽  
Axel A. Brakhage ◽  
Hubertus Haas
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Homeostasis

Effects of the Aspergillus fumigatus siderophore systems on the regulation of macrophage immune effector pathways and iron homeostasis

Immunobiology ◽  
2008 ◽  
Vol 213 (9-10) ◽  
pp. 767-778 ◽  
Author(s):  
M. Seifert ◽  
M. Nairz ◽  
A. Schroll ◽  
M. Schrettl ◽  
H. Haas ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Homeostasis ◽  
Immune Effector ◽  
Effector Pathways

scholarly journals Dual-purpose isocyanides produced by Aspergillus fumigatus contribute to cellular copper sufficiency and exhibit antimicrobial activity

2021 ◽  
Vol 118 (8) ◽  
pp. e2015224118
Author(s):  
Nicholas Raffa ◽  
Tae Hyung Won ◽  
Andrew Sukowaty ◽  
Kathleen Candor ◽  
Chengsen Cui ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Inductively Coupled Plasma ◽  
Iron Homeostasis ◽  
Antimicrobial Properties ◽  
Pathogenic Fungi ◽  
Biosynthetic Gene Cluster ◽  
Mass Spectrometry Analysis ◽  
Copper Binding ◽  
Spectrometry Analysis ◽  
Cellular Copper

The maintenance of sufficient but nontoxic pools of metal micronutrients is accomplished through diverse homeostasis mechanisms in fungi. Siderophores play a well established role for iron homeostasis; however, no copper-binding analogs have been found in fungi. Here we demonstrate that, in Aspergillus fumigatus, xanthocillin and other isocyanides derived from the xan biosynthetic gene cluster (BGC) bind copper, impact cellular copper content, and have significant metal-dependent antimicrobial properties. xan BGC-derived isocyanides are secreted and bind copper as visualized by a chrome azurol S (CAS) assay, and inductively coupled plasma mass spectrometry analysis of A. fumigatus intracellular copper pools demonstrated a role for xan cluster metabolites in the accumulation of copper. A. fumigatus coculture with a variety of human pathogenic fungi and bacteria established copper-dependent antimicrobial properties of xan BGC metabolites, including inhibition of laccase activity. Remediation of xanthocillin-treated Pseudomonas aeruginosa growth by copper supported the copper-chelating properties of xan BGC isocyanide products. The existence of the xan BGC in several filamentous fungi suggests a heretofore unknown role of eukaryotic natural products in copper homeostasis and mediation of interactions with competing microbes.

scholarly journals Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin

Genetics ◽  
2021 ◽  
Author(s):  
Ana Cristina Colabardini ◽  
Fang Wang ◽  
Zhiqiang Dong ◽  
Lakhansing Pardeshi ◽  
Marina Campos Rocha ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Antifungal Agent ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Invasive Pulmonary Aspergillosis ◽  
Transcriptional Response ◽  
Cell Wall Remodeling

Abstract Aspergillus fumigatus is the main causative agent of invasive pulmonary aspergillosis (IPA), a severe disease that affects immunosuppressed patients worldwide. The fungistatic drug caspofungin is the second line of therapy against IPA but has increasingly been used against clinical strains that are resistant to azoles, the first line antifungal therapy. In high concentrations, caspofungin induces a tolerance phenotype with partial reestablishment of fungal growth called caspofungin paradoxical effect (CPE), resulting from a change in the composition of the cell wall. An increasing number of studies has shown that different isolates of A. fumigatus exhibit phenotypic heterogeneity, including heterogeneity in their CPE response. To gain insights into the underlying molecular mechanisms of CPE response heterogeneity, we analyzed the transcriptomes of two A. fumigatus reference strains, Af293 and CEA17, exposed to low and high caspofungin concentrations. We found that there is a core transcriptional response that involves genes related to cell wall remodeling processes, mitochondrial function, transmembrane transport, and amino acid and ergosterol metabolism, and a variable response related to secondary metabolite (SM) biosynthesis and iron homeostasis. Specifically, we show here that the overexpression of a SM pathway that works as an iron chelator extinguishes the CPE in both backgrounds, whereas iron depletion is detrimental for the CPE in Af293 but not in CEA17. We next investigated the function of the transcription factor CrzA, whose deletion was previously shown to result in heterogeneity in the CPE response of the Af293 and CEA17 strains. We found that CrzA constitutively binds to and modulates the expression of several genes related to processes involved in caspofungin tolerance, and that crzA deletion differentially impacts the SM production and growth of Af293 and CEA17. As opposed to the ΔcrzACEA17 mutant, the ΔcrzA Af293 mutant fails to activate cell wall remodeling genes upon caspofungin exposure, which most likely severely affects its macrostructure and extinguishes its CPE. This work describes how heterogeneity in the response to an antifungal agent between A. fumigatus strains stems from heterogeneity in the function of a transcription factor and its downstream target genes.

scholarly journals Iron homeostasis—Achilles’ heel of Aspergillus fumigatus?

2011 ◽  
Vol 14 (4) ◽  
pp. 400-405 ◽  
Author(s):  
Markus Schrettl ◽  
Hubertus Haas
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Homeostasis

scholarly journals Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus

Virulence ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 1036-1049 ◽  
Author(s):  
Anna-Maria Dietl ◽  
Zohar Meir ◽  
Yona Shadkchan ◽  
Nir Osherov ◽  
Hubertus Haas
Keyword(s):  
Aspergillus Fumigatus ◽  
Iron Homeostasis ◽  
Pantothenic Acid ◽  
Acid Biosynthesis

scholarly journals Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Benoit Briard ◽  
Perrine Bomme ◽  
Beatrix E. Lechner ◽  
Gaëtan L. A. Mislin ◽  
Virginie Lair ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aspergillus Fumigatus ◽  
Iron Homeostasis

scholarly journals Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin

2021 ◽  
Author(s):  
Ana Cristina Colabardini ◽  
Fang Wang ◽  
Zhiqiang Dong ◽  
Lakhansing Pardeshi ◽  
Marina C Rocha ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Antifungal Agent ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Invasive Pulmonary Aspergillosis ◽  
Transcriptional Response ◽  
Cell Wall Remodeling

Aspergillus fumigatus is the main causative agent of invasive pulmonary aspergillosis (IPA), a severe disease that affects immunosuppressed patients worldwide. The fungistatic drug caspofungin is the second line therapy against IPA but has increasingly been used against clinical strains that are resistant to azoles, the first line antifungal therapy. In high concentrations, caspofungin induces a tolerance phenotype with partial reestablishment of fungal growth called caspofungin paradoxical effect (CPE), resulting from a change in the composition of the cell wall. An increasing number of studies has shown that different isolates of A. fumigatus exhibit phenotypic heterogeneity, including heterogeneity in their CPE response. To gain insights into the underlying molecular mechanisms of CPE response heterogeneity, we analyzed the transcriptomes of two A. fumigatus reference strains, Af293 and CEA17, exposed to low and high caspofungin concentrations. We found that there is a core transcriptional response that involves genes related to cell wall remodeling processes, mitochondrial function, transmembrane transport, and amino acid and ergosterol metabolism, and a variable response related to secondary metabolite (SM) biosynthesis and iron homeostasis. Specifically, we show here that the overexpression of a SM pathway that works as an iron chelator extinguishes the CPE in both backgrounds, whereas iron depletion is detrimental for the CPE in Af293 but not in CEA17. We next investigated the function of the transcription factor CrzA, whose deletion was previously shown to result in heterogeneity in the CPE response of the Af293 and CEA17 strains. We found that CrzA constitutively binds to and modulates the expression of several genes related to processes involved in caspofungin tolerance, and that crzA deletion differentially impacts the SM production and growth of Af293 and CEA17. As opposed to the ? crzA CEA17 mutant, the ? crzA Af293 mutant fails to activate cell wall remodeling genes upon caspofungin exposure, which most likely severely affects its macrostructure and extinguishes its CPE. This work describes how heterogeneity in the response to an antifungal agent between A. fumigatus strains stems from heterogeneity in the function of a transcription factor and its downstream target genes.

scholarly journals Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines

2015 ◽  
Vol 25 (2) ◽  
pp. e106
Author(s):  
Benoit Briard ◽  
Perrine Bomme ◽  
Beatrix Lechner ◽  
Gaëtan Mislin ◽  
Virginie Lair ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Aspergillus Fumigatus ◽  
Iron Homeostasis
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