Exploring the Siderophore\nPortfolio for Mass Spectrometry-Based\nDiagnosis of Scedosporiosis and Lomentosporiosis

Scedosporium\napiospermum and Lomentospora prolificans secrete\nsiderophores (iron\nscavengers) during hyphal proliferation. Siderophores are virulence\nfactors and potential clinical biomarkers of invasive scedosporiosis\nand lomentosporiosis. Both strains secreted a uniform spectrum of\nsiderophores, including coprogen B (CopB), <i>N</i><sup>α</sup>-methyl-coprogen B, dimethyl-coprogen, and ferricrocin,\nwith <i>N</i><sup>α</sup>-methyl-coprogen B being\nthe fastest secreted and most abundant coprogen. Under iron and zinc\nrestriction, reflecting a nutrient-limited host environment, L. prolificans secreted 45 times more CopB than did S. apiospermum, presumably contributing to its higher\nvirulence. This robust mobilization of CopB was further enhanced by\nzinc surplus. Additionally, two novel cyclic peptides, Scedocyclin\nA and B, were characterized inScedosporium boydii using the <i>de novo</i> sequencing tool CycloBranch.\nUtilizing matrix-assisted laser desorption/ionization, the portfolio\nof coprogens detected had limits of detection and quantitation of\n4.9 and 14.6 fmol/spot in complex matrices, respectively, making them\nstrong candidates for the next-generation, routine diagnosis of invasive\nscedosporiosis and lomentosporiosis through the Biotyper siderotyping.