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Significance The opportunistic fungal pathogenCryptococcus neoformans is a major threat to immunocompromised patients. Most fungal cell walls expose chitin, which is recognized by the human immune system, butC. neoformans is one of the few species that instead exposes chitosan, the deacetylated form of chitin. Chitosan is produced by chitin synthases and chitin deacetylases, the latter acting on chitin as a substrate. Here we describe the detailed functional analysis of CnCda4, a chitin deacetylase with unusual subsite specificity resulting in a preference for chitosan rather than chitin. By testing the effect of CnCda4 deacetylation products on human peripheral blood-derived macrophages, we show that the enzyme probably helps the pathogen to evade the host immune system by further deacetylating exposed chitosans.

Unique subsite specificity and potential natural function of a chitosan deacetylase from the human pathogen Cryptococcus neoformans