Abstract
The saprophytic fungus Aspergillus fumigatus is the most important air-borne fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a potential target for development of effective antifungal agents. A major role in maintaining cell wall integrity is played by the mitogen-activated protein kinase (MAPK) MpkA. To gain a comprehensive insight into this central signal transduction pathway, we performed a transcriptome analysis of the ΔmpkA mutant under standard and cell wall stress conditions. Besides genes involved in cell wall remodelling, protection against ROS and secondary metabolism such as gliotoxin, pyomelanin and pseurotin A, also genes involved in siderophore biosynthesis were regulated by MpkA. Consistently, northern and western blot analyses indicated that iron starvation triggers phosphorylation and thus activation of MpkA. Furthermore, localization studies indicated that MpkA accumulates in the nucleus under iron depletion. Hence, we report the first connection between a MAPK pathway and siderophore biosynthesis. The measurement of amino acid pools and of the pools of polyamines indicated that arginine was continuously converted into ornithine to fuel the siderophore pool in the ΔmpkA mutant strain. Based on our data, we propose that MpkA fine-tunes the balance between stress response and energy consuming cellular processes.
Highlights
Responding to external signals and adaptation to changes in the environment is indispensable for the viability of all organisms
It has emerged to be the most common fungal pathogen causing invasive aspergillosis (IA) in immunocompromised patients (Brakhage, 2005; Dagenais and Keller, 2009; Brakhage et al, 2010). Fungal pathogens such as A. fumigatus employ signal transduction cascades including mitogen-activated protein kinase (MAPK) pathways to sense, transduce and regulate different developmental processes of the fungal cell in response to extracellular cues (Rispail et al, 2009)
It is involved in response to reactive oxygen species (ROS) and affects the formation of pyomelanin derived from tyrosine degradation (Valiante et al, 2008; 2009)
Summary
Responding to external signals and adaptation to changes in the environment is indispensable for the viability of all organisms. Aspergillus fumigatus, a saprophytic fungus, is able to grow and proliferate in a variety of environments (Tekaia and Latgé, 2005) It can colonize the human body where it is challenged by diverse physical and chemical conditions, such as presence of cell walldegrading enzymes, oxidizing agents, limited nutrient availability, or changing pH, osmolarity and temperature. It has emerged to be the most common fungal pathogen causing invasive aspergillosis (IA) in immunocompromised patients (Brakhage, 2005; Dagenais and Keller, 2009; Brakhage et al, 2010) Fungal pathogens such as A. fumigatus employ signal transduction cascades including mitogen-activated protein kinase (MAPK) pathways to sense, transduce and regulate different developmental processes of the fungal cell in response to extracellular cues (Rispail et al, 2009).
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