Increased Amounts of the Aspergillus Metabolite D-Mannitol in Tissue and Serum of Rats with Experimental Aspergillosis

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Abstract
Several Aspergillus species produce large amounts of the hexitol d-rnannitol in vitro, but it is not known whether these species also produce d-rnannitol in vivo. Serum samples and homogenized tissues were analyzed from rats pretreated with cortisone and cyclophosphamide and then given 2 × 106 preincubated conidia of Aspergillus jumigatus intravenously. The resulting infection was lethal by 48 h and was characterized by much more severe disease in the liver than in the kidneys, spleen, or lungs. A compound present in increased amounts in the livers and sera of the infected rats was shown to be d-mannitol by gas chromatography (GC) and GC/mass spectrometry and enzymatically. Quantitative analysis by GC showed that the infected rats had more d-mannitol in their livers (but not in their lungs or kidneys) after 12 h (P < .01 at 12, 24, and 36 h) and higher serum d-mannitol concentrations and serum d-mannitol/creatinine ratios after 36 h (P < .05) than did uninfected controls. These results indicate that A. jumigatus can produce and release sufficient d-mannitol in the tissues of infected animals to raise serum d-mannitol levels. Thus, d-mannitol is a potential diagnostic marker for aspergillosis.