VARIATION IN THE STRUCTURE OF GLUCURONOXYLOMANNAN IN ISOLATES FROM PATIENTS WITH RECURRENT CRYPTOCOCCAL MENINGITIS

Capsular glucuronoxylomannans (GXM) of Cryptococcus neoformans var, ne oformans isolates from patients with recurrent cryptococcal meningitis were analyzed by H-1 nuclear magnetic resonance spectroscopy and for reactivity with factor sera (latron, Tokyo, Japan); For each patient t he initial and relapse isolates had previously been shown to be indist inguishable by DNA restriction fragment length polymorphism analysis, For patients J11 and J22 the GXM of the initial and relapse isolates w ere identical. For patients SB4 and SB6 the GXM of the initial and rel apse isolates differed in structure and reactivity with factor sera, I n patient SB4 the initial isolate had a serotype A/D structure, and th e first relapse isolate had a serotype A structure. The second relapse isolate was a mixture of structures composed of serotype D components , glucuronomannan (GM), and a minor serotype A component. Analysis of the initial isolate from patient SB6 showed a structure composed mainl y of serotype D, GM, and minor serotype A components and components no t assigned to a particular serotype (N). The relapse isolate had the s ame composition as the initial isolate except for an increase in the s erotype A component. This increase in the serotype A component of the relapse isolate resulted in a change in the serological specificity fr om serotype D to serotype A/D. The initial isolate from patient J9 had serotype D and GM structures. The first two relapse isolates had sero type D, N, and GM structures and a minor serotype A component. The thi rd relapse isolate had mainly a serotype D structure. All the J9 isola tes reacted only with serotype D-specific factor serum. These results indicate that some isolates obtained from patients with recurrent C. n eoformans infections have undergone a change in GXM structure during t he course of infection. The modification of GXM structure observed in some relapse isolates is reflected in changed serological properties. The results may have important implications for the design of vaccines and antibody-based therapeutic strategies against C. neoformans.