D-arabinitol is a major metabolite of the medically important Candida species, and animals and humans with invasive candidiasis have higher serum and urinary arabinitol/creatinine ratios than uninfected controls. This is a proposal to study D-arabinitol further as a diagnostic marker for candidiasis. Two methods will be developed to measure D-arabinitol stereoselectively in body fluids and tissue homogenates. One approach will be to measure D,L-arabinitol by gas chromatography (GC) in portions of each specimen that are treated with and without the Klebsiella pneumoniae NAD: oxidoreductase D-arabinitol dehydrogenase (ADH); insofar as ADH degrades D-arabinitol completely and stereoselectively, the difference can be considered the D- enantiomer. A second approach will be to resolve D- from L- arabinitol by multidimensional GC with a conventional and chiral capillary column in series; the enantiomers will then be quantified individually. These stereoselective analytical methods will then be used to study the effects on D-arabinitol appearance of the diet, microbial colonization of the gastrointestinal tract, host metabolism, corticosteroids and sarcoidosis in animals and/or humans without invasive candidiasis. The diagnostic sensitivity and specificity of elevated D-arabinitol/creatinine ratios will be studied prospectively in high risk patients and using stored specimens previously collected from infected animals and humans. D-arabinitol measurements will also be compared to tests for anti-Candida antibodies and for Candida antigens. Lastly, whether the effects of antifungal therapy can be assessed quantitatively be serial D-arabinitol measurements will be studied in rats with experimental candidiasis.
