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Exploring the Siderophore Portfolio for Mass Spectrometry-Based Diagnosis of Scedosporiosis and Lomentosporiosis

Summary

Two dangerous opportunistic fungi that cause serious infections in vulnerable patients produce distinct chemical compounds called siderophores to help them acquire iron from their hosts. Researchers used advanced mass spectrometry techniques to detect and measure these compounds, finding that one fungus produces significantly more of these iron-scavenging molecules, which may explain why it causes more severe infections. These siderophores could potentially be used as diagnostic markers in medical laboratories to quickly identify these infections in patient samples.

Background

Scedosporium apiospermum and Lomentospora prolificans are opportunistic fungal pathogens listed as WHO priority pathogens that are intrinsically resistant to antifungals and cause invasive infections with high mortality rates in immunocompromised patients. Siderophores are iron-scavenging virulence factors secreted during fungal proliferation and represent potential clinical biomarkers for invasive mycoses.

Objective

To characterize and compare the siderophore portfolio of S. apiospermum and L. prolificans under various iron and zinc stress conditions, and to evaluate siderophores as mass spectrometry-based diagnostic biomarkers for invasive scedosporiosis and lomentosporiosis.

Results

Both strains secreted uniform siderophore spectra including coprogen B, N-methyl-coprogen B, dimethyl-coprogen, and ferricrocin, with L. prolificans producing 45-fold more coprogen B under iron-zinc restriction. MALDI+ analysis achieved superior detection limits (4.9 fmol/spot) compared to LC-MS-ESI+. Two novel cyclic peptides, Scedocyclin A and B, were characterized in S. boydii.

Conclusion

Siderophores, particularly coprogens, are strong candidates for next-generation routine diagnosis of invasive scedosporiosis and lomentosporiosis through Biotyper siderotyping, with MALDI+ offering superior sensitivity for clinical applications.
  • Published in:ACS Omega,
  • Study Type:Experimental Study,
  • Source: 10.1021/acsomega.4c08257, PMID: 39524635
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