Variation in the structure of glucuronoxylomannan in isolates from patients with recurrent cryptococcal meningitis

Abstract

Capsular glucuronoxylomannans (GXM) of Cryptococcus neoformans var. neoformans isolates from patients with recurrent cryptococcal meningitis were analyzed by 1H nuclear magnetic resonance spectroscopy and for reactivity with factor sera (Iatron, Tokyo, Japan). For each patient the initial and relapse isolates had previously been shown to be indistinguishable by DNA restriction fragment length polymorphism analysis. For patients J11 and J22 the GXM of the initial and relapse isolates were identical. For patients SB4 and SB6 the GXM of the initial and relapse isolates differed in structure and reactivity with factor sera. In patient SB4 the initial isolate had a serotype A/D structure, and the 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 mainly of serotype D, GM, and minor serotype A components and components not assigned to a particular serotype (N). The relapse isolate had the same composition as the initial isolate except for an increase in the serotype A component. This increase in the serotype A component of the relapse isolate resulted in a change in the serological specificity from serotype D to serotype A/D. The initial isolate from patient J9 had serotype D and GM structures. The first two relapse isolates had serotype D, N, and GM structures and a minor serotype A component. The third relapse isolate had mainly a serotype D structure. All the J9 isolates reacted only with serotype D-specific factor serum. These results indicate that some isolates obtained from patients with recurrent C. neoformans infections have undergone a change in GXM structure during the 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.