Abstract
The ubiquitous mold Scedosporium apiospermum is increasingly recognized as an emerging pathogen, especially among patients with underlying disorders such as immunodeficiency or cystic fibrosis (CF). Indeed, it ranks the second among the filamentous fungi colonizing the respiratory tract of CF patients. However, our knowledge about virulence factors of this fungus is still limited. The role of iron-uptake systems may be critical for establishment of Scedosporium infections, notably in the iron-rich environment of the CF lung. Two main strategies are employed by fungi to efficiently acquire iron from their host or from their ecological niche: siderophore production and reductive iron assimilation (RIA) systems. The aim of this study was to assess the existence of orthologous genes involved in iron metabolism in the recently sequenced genome of S. apiospermum. At first, a tBLASTn analysis using A. fumigatus iron-related proteins as query revealed orthologs of almost all relevant loci in the S. apiospermum genome. Whereas the genes putatively involved in RIA were randomly distributed, siderophore biosynthesis and transport genes were organized in two clusters, each containing a non-ribosomal peptide synthetase (NRPS) whose orthologs in A. fumigatus have been described to catalyze hydroxamate siderophore synthesis. Nevertheless, comparative genomic analysis of siderophore-related clusters showed greater similarity between S. apiospermum and phylogenetically close molds than with Aspergillus species. The expression level of these genes was then evaluated by exposing conidia to iron starvation and iron excess. The expression of several orthologs of A. fumigatus genes involved in siderophore-based iron uptake or RIA was significantly induced during iron starvation, and conversely repressed in iron excess conditions. Altogether, these results indicate that S. apiospermum possesses the genetic information required for efficient and competitive iron uptake. They also suggest an important role of the siderophore production system in iron uptake by S. apiospermum.
Highlights
Iron is the fourth most common element found on the Earth’s crust (Frey and Reed, 2012)
This strategy allowed to find orthologs of all genes involved in iron acquisition and storage (Table 1), with the exception of srbA, which encodes a regulatory protein that activates iron uptake during iron deprivation (Blatzer et al, 2011a), sidG, which encodes a protein that catalyzes fusarinine C esterification, and estB and sidJ, which both encode proteins involved in triacetylfusarinine C saponification (Kragl et al, 2007; Schrettl et al, 2007)
The “battle for iron” between a given pathogen and the host, and between several pathogens coexisting within the same host (e.g., A. fumigatus and Pseudomonas aeruginosa in the cystic fibrosis (CF) lung), is a key determinant for a successful infection
Summary
Iron is the fourth most common element found on the Earth’s crust (Frey and Reed, 2012). In spite of its abundance, iron is fairly accessible to living organisms as a result of its very limited solubility under aerobic conditions. Iron is mainly encountered in two relatively stable oxidation states, ferrous (Fe(II) or Fe2+) and ferric (Fe(III) or Fe3+). Due to the reversible switching between the Fe2+ and Fe3+ species and its ability to form coordination complexes with organic ligands, iron plays a critical role in numerous biochemical processes including oxidative phosphorylation, DNA replication, and biosynthesis of small molecules such as lipids, amino acids, and sterols (Philpott, 2006). Iron excess can be harmful to the cell owing to its capacity to catalyze the formation of reactive oxygen species (ROS) and to initiate lipid peroxidation (Halliwell and Gutteridge, 1984). Microbes have evolved sophisticated systems to overcome suboptimal iron availability and to prevent iron overload toxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
