Glucuronoxylomannan of Cryptococcus neoformans obtained from patients with AIDS

Abstract

Cryptococcus neoforrnans has emerged as a major opportunistic pathogen in patients diagnosed with acquired immunodeficiency syndrome (AIDS)‘. The yeast has a predilection for the central nervous system, where it causes cryptococcal meningoencephalitis*. In the pre-AIDS era both varieties of C. neofomans (C. neoformans var. neoformans and C. neoformans var. guttii) were isolated from clinical specimens3, whereas today C. neofomans isolates from AIDS patients are almost invariably of the neofomans variety 4s There appears to be a selective . infection of AIDS patients with the neofomam variety and 99% of these are of the A serotype ‘7’ The results of our comprehensive investigation of the major . capsular polysaccharide of C. neofomans serotype A revealed structural variability between isolates’,‘. Of the eleven isolates studied, six (Group I’) conformed closely to the model originally proposed by Merrifield and Stephen” and Bhattacharjee et al. l1 Two isolates (Group II’) are deficient in xylose to the extent . that, based on molar ratios, they could easily be classified as serotype D’*-14 or A-D15. However, both 13C NMR spectroscopy and methylation analysis clearly indicated that the two isolates of Group II differed from the typical D and A-D glucuronoxylomannans (GXM). The Group II GXMs have a significant quantity (10%) of Manp residues substituted with GlcpA at O-2 and Xylp at O-4 whereas serotype D and A-D isolates do not. The Group II isolates were later confirmed to be serotype A9 by using specific rabbit antisera (J.E. Bennett, National Institutes of Health). The remaining two groups, III and IV, contained substantial amounts of linkages thought to be distinctive of serotypes B’6-1s and C19y20, i.e., Manp that are 40glycosylated with B-D-Xylp, while still possessing unsubstituted (1 --, 3)-(YD-Manp.