Resumo

Cryptococcus neoformans is the causative agent of cryptococcal meningitis, the most serious clinical form of cryptococcosis in immunosupressed patients. The most important virulence factor of C. neoformans is glucuronoxylomannan (GXM), a high molecular mass polysaccharide that is continuously secreted to subvert the host immune response (Med Mycol. 1; 2009). The mechanisms by which GXM interferes with the physiology of the central nervous system are virtually unknown. In this context, we asked whether GXM would interfere with the activities of acetylcholinesterase (AChE) and choline acetyl- transferase (ChAT). A dose-dependent activation of ChAT was observed when enzyme activity was assayed in the presence of GXM. On the other hand, AChE was strongly inhibited in the presence of the fungal polysaccharide. Both inhibitory and activation effects were clearly reverted in the presence of a monoclonal antibody raised against GXM, confirming the specificity of the effects promoted by the polysaccharide. These results suggest a new mechanism by which the key virulence factor of C. neoformans could interfere with host’s physiology and show a previously unknown regulation of acetylcholine metabolism by a microbial polysaccharide.