Inducible hydrolases in the pathogenesis and serodiagnosis of systemic candidosis.

The aim of this study was to search for inducible hydrolytic enzymes of Candida albicans, to investigate any link between such enzymes and the pathogenesis of candidosis - a potentially fatal disease with a poor prognosis - and to test these enzymes as infection-specific antigens in the serological diagnosis of deep-seated infection. No inducible hyaluronidase or phospholipases could be detected under the conditions employed. An acid proteinase, found in the culture filtrates of C.albicans grown at 26C in a medium based on glucose and bovine serum albumin, was purified by a one-step chromatographic method. The enzyme was judged to be pure by serological and biochemical tests. It was shown to be a glycoprotein, containing 1.5% mannan, and to belong to the carboxyl proteinases. Proteinase was detected in greatest amounts in the most virulent of the pathogenic members of the genus Candida. It was secreted in vivo and was detected by indirect fluorescent antibody techniques around C.albicans blasto- spores in kidney microabscesses of experimentally infected mice. Purified proteinase appeared to be a very specific antigen when tested against sera from experimentally infected rabbits, since no anti-proteinase precipitins were detected in the sera of those rabbits in which tissue invasion was prevented by treatment with ketoconazole. Precipitin titres to purified proteinase exceeded 1:4 in 77% of sera from 13 patients with proven systemic Candida infection, in 23% of sera from 22 patients positive for Candida anticytoplasm antibodies but without corroborative diagnostic evidence of systemic candidosis, and in none of 28 sera from patients without either candidosis or anti-cytoplasm antibodies. Although the results did not confirm unequivocally the role of proteinase as a factor in the virulence of C.albicans, they gave considerable support to this idea. Purified proteinase was not a qualitatively specific antigen for the serological diagnosis of candidosis, but it was shown to give quantitatively superior results to those obtained with traditional cytoplasmic extracts of the fungus.