Non-invasive and invasive diagnoses of aspergillosis in a rat model by mass spectrometry.

Abstract

Invasive pulmonary aspergillosis results in 450,000 deaths per year and complicates cancer chemotherapy, transplantations and the treatment of other immunosuppressed patients. Using a rat model of experimental aspergillosis, the fungal siderophores ferricrocin and triacetylfusarinine C were identified as markers of aspergillosis and quantified in urine, serum and lung tissues. Biomarkers were analyzed by matrix-assisted laser desorption ionization (MALDI) and electrospray ionization mass spectrometry using a 12T SolariX Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. The limits of detection of the ferri-forms of triacetylfusarinine C and ferricrocin in the rat serum were 0.28 and 0.36 ng/mL, respectively. In the rat urine the respective limits of detection achieved 0.02 and 0.03 ng/mL. In the sera of infected animals, triacetylfusarinine C was not detected but ferricrocin concentration fluctuated in the 3-32 ng/mL range. Notably, the mean concentrations of triacetylfusarinine C and ferricrocin in the rat urine were 0.37 and 0.63 μg/mL, respectively. The MALDI FTICR mass spectrometry imaging illustrated the actual microbial ferricrocin distribution in the lung tissues and resolved the false-positive results obtained by the light microscopy and histological staining. Ferricrocin and triacetylfusarinine C detection in urine represents an innovative non-invasive indication of Aspergillus infection in a host.

• Authors: Dominika Luptáková, Tomáš Pluháček, Miloš Petřík, Jiří Novák, Andrea Palyzová, Lucie Sokolová, Anton Škríba, Blanka Šedivá, Karel Lemr, Vladimír Havlíček
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 16523 (11 28 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 29184111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Siderophores

Topics

• Animals
• Aspergillosis (diagnosis, microbiology)
• Aspergillus (chemistry, metabolism)
• Biomarkers
• Chromatography, Liquid
• Colony Count, Microbial
• Disease Models, Animal
• Histocytochemistry
• Humans
• Invasive Pulmonary Aspergillosis (diagnosis, microbiology)
• Lung (microbiology, pathology)
• Mass Spectrometry (methods)
• Metabolomics (methods)
• Rats
• Siderophores (analysis, chemistry)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)