Polysaccharide capsules surround many fungal pathogens and contribute to virulence by inhibiting complement-mediated phagocytosis. By purifying polysaccharide capsule-associated proteins, Park et al. found a new Cryptococcus neoformans enzyme — the lactonohydrolase LHC1 — and showed that it is involved in the higher-order assembly of this structure. Mutant strains that lack LHC1 have a larger capsule than wild-type strains and have altered polysaccharide branching; the larger capsule is more permeable to anti-capsular antibodies and more susceptible to opsonization by both mouse and human complement. These alterations led to increased phagocytosis of fungi that lacked LHC1, which correlated with decreased virulence of the mutant strains in mice. These results establish LHC1 as a new C. neoformans virulence factor that functions by introducing modifications in capsular structure that prevent fungal detection by the immune system.
Park, Y.-D. et al. A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule. PLoS Pathog. http://dx.doi.org/10.1371/journal.ppat.1004037 (2014)
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BMC Bioinformatics (2015)