A Role for in Higher Order Structure and Complement Binding of the Capsule

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Polysaccharide capsules are important virulence factors in pathogenic microbes that provide a protective coat against host immunity. Cryptococcus neoformans is a pathogenic encapsulated yeast that is a major opportunistic infection, causing approximately 600,000 cases of meningitis per year in AIDS patients globally, and whose polysaccharide capsule is a major virulence factor. While extensive work has detailed the chemical components forming the cryptococcal capsule, the molecular events leading to the higher order assembly of the capsule, and its consequences on immune subterfuge remain unknown. In the present studies we used a proteomics method to identify a novel hydrolytic enzyme, lactonohydrolase (Lhc1) and used a variety of biophysical methods including dynamic and static light scattering as well as motility studies to show that extracted capsular polysaccharide undergoes remodeling in a LHC1-dependent fashion. This results in a more tightly compacted capsular structure that alters binding of anti-capsular antibodies and reduces binding by both human as well as mouse serum complement. Furthermore, LHC1-dependent capsular alterations serve to increase the virulence of the fungus in a mouse model, suggesting a novel role for this class of enzyme in capsular remodeling and immune evasion in microbial pathogenesis.

Vyšlo v časopise: A Role for in Higher Order Structure and Complement Binding of the Capsule. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004037
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004037

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