Paper appeared: “Unique subsite specificity and potential natural function of a chitosan deacetylase from the human pathogen Cryptococcus neoformans“
Already on January 3rd, Lea Hembach’s paper on the first ever chitosan deacetylase and its proposed role in the virulence of the human pathogenic fungus Cryptococcus neoformans was accepted for publication in the highly renowned Proceedings of the National Academy of Sciences of the USA - PNAS. This fungus can cause cryptococcal meningitis, particularly in immuno-compromised patients, annually leading to more than 180,000 deaths worldwide. We became interested in this fungus when it was reported to use a similar stealth strategy to evade its host’s immune system as we had earlier reported for the wheat stem rust fungus, namely conversion of the tell-tale cell wall chitin into less immuno-stimulatory chitosan. The genome of C. neoformans contains four putative chitin deacetylases, but only three of them had been confirmed as such. Lea heterologously expressed the fourth gene in E. coli and found it to be a chitosan hydrolase, i.e. a deacetylase that prefers partially acetylated chitosan over fully acetylated chitin as a substrate. Together with then Master candidate Martin Bonin, she identified the structural characteristics which are responsible for this unusual substrate preference, and together with our collaborator Dr. Christian Gorzelanny at the University Hospital Eppendorf in Hamburg, she found evidence that this enzyme is responsible for the abolition of residual immuno-stimulatory activity of the fungal chitosan. Thus, inhibiting this enzyme could be a promising strategy to help the human immune system coping with this potentially fatal pathogen.