Background: Fusarium species cause severe, life-threatening infections in immunocompromised patients. Early diagnosis is critical due to the propensity of these species for adventitious sporulation and systemic dissemination, but difficult clinically due to the lack of specific, rapid, noninvasive diagnostic methods.
Methods: We examined the volatile organic metabolite profile of five common pathogenic Fusarium species in vitro, identifying key volatile organic metabolites (VOCs) using thermal desorption-gas chromatography (GC)/tandem mass spectrometry (MS), in parallel with GC-differential mobility spectrometry (DMS). DMS provides a rapid, portable method of identifying particular volatile metabolites in complex gas mixtures based on atmospheric pressure ionization followed by differential trajectories of these ion species across an asymmetric waveform electrical field.
Results: We identified a unique pattern of volatile secondary sesquiterpene metabolites for each Fusarium species by GC-MS, with corresponding identification of these species-specific metabolite signatures by GC-DMS. Fusarium solani (N = 5) emitted a signature of isocomene, farnesene, isocaryophyllene, and aciphyllene (Figure 1: left panel: representative GC-MS total ion chromatogram segment of relative abundance (total ion count) vs. retention time), right panel: representative GC-DMS plot of DMS metabolite intensity vs. VC (compensation voltage) vs. retention time). F. verticillioides (N = 4) produced cubenene, valencene, and acoradiene (Figure 2), F. proliferatum (N = 7) produced acora-3,7(14)-diene, himachalene, alloaromadendrene, and acoradiene (Figure 3), and F. oxysporum (N = 5) produced valencene and acoradiene.
species produce unique secondary volatile metabolite signatures that are
distinct from the volatile metabolite signatures of Aspergillus, Scedosporium/Lomentospora,
and common pathogenic Mucorales. These fungal
metabolite signatures may be used as targets for rapid, breath-based
identification of Fusarium
infections and allow differentiation from other invasive mold infections.
Figure 1. Fusarium solani.
Figure 2. Fusarium verticillioides.
Figure 3. Fusarium proliferatum.
O. Aloum, None
L. R. Baden, None
F. M. Marty, Alexion: Scientific Advisor , Consulting fee
Ansun: Investigator , Research support
Astellas: Consultant and Investigator , Consulting fee and Research support
Basilea: Conference speaker , Speaker honorarium
Chimerix: Consultant and Investigator , Consulting fee and Research support
Gilead: Consultant and Investigator , Consulting fee and Research support
GlaxoSmithKline: Consultant and Investigator , Consulting fee and Research grant
LFB, S.A.: Consultant , Consulting fee
Merck: Consultant and Investigator , Consulting fee and Research support
Shire: Consultant and Investigator , Consulting fee and Research support
WHISCON: Investigator , Research support
Pfizer: Course speaker , Speaker honorarium
Fate Therapeutics: Scientific Advisor , Consulting fee
N. Wiederhold, BioMerieux: Grant Investigator , Research support
S. Koo, Wako Diagnostics: Grant Investigator , Research support