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

Several Aspergillus species produce large amounts of the hexitol D-mannitol in vitro, but it is not known whether these species also produce D-mannitol in vivo. Serum samples and homogenized tissues were analyzed from rats pretreated with cortisone and cyclophosphamide and then given 2 x 10(6) preincubated conidia of Aspergillus fumigatus 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 less than .01 at 12, 24, and 36 h) and higher serum D-mannitol concentrations and serum D-mannitol/creatinine ratios after 36 h (P less than .05) than did uninfected controls. These results indicate that A. fumigatus 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.