Glucuronoxylomannan fromCryptococcus neoformans Down-regulates the Enzyme 6-Phosphofructo-1-kinase of

is coated by a polysaccharide capsulemainly composed of glucuronoxylomannan (GXM). GXM isconsidered a key virulence factor of this pathogen. The presentwork aimed at evaluating the effects of GXM on the key glyco-lytic enzyme, 6-phosphofructo-1-kinase (PFK). GXM inhibitedPFKactivityinculturedmurinemacrophagesinbothdose-andtime-dependentmanners,whichoccurredinparalleltocellvia-bilitydecrease.ThepolysaccharidealsoinhibitedpurifiedPFK,promoting a decrease on the enzyme affinity for its substrates.In macrophages GXM and PFK partially co-localized, suggest-ing that internalized polysaccharide directly may interact withthis enzyme. The mechanism of PFK inhibition involved disso-ciation of tetramers into weakly active dimers, as revealed byfluorescencespectroscopy.Allostericmodulatorsoftheenzymeable to stabilize its tetrameric conformation attenuated theinhibition promoted by GXM. Altogether, our results suggestthat the mechanism of GXM-induced cell death involves theinhibition of the glycolytic flux.