Discordant regulation of phenoloxidase and capsular polysaccharide in Cryptococcus neoformans

We examined the regulation of two fungal virulence factors, phenoloxidase and capsular polysaccharide, in an ex-type strain of the fungal pathogen, Cryptococcus neoformans. Both were made during the stationary phase of cultural growth. Exogenous iron increased phenoloxidase activity three-fold (from 8.7 to 27.7 units mg-1, P < 0.05) but decreased capsular polysaccharide three-fold (from 9.0 to 3.4% packed cell volume, P < 0.01). A temperature shift from 25 to 37 degrees C decreased phenoloxidase activity three-fold (from 60.6 to 23.7 units mg-1, P < 0.01) but not capsular polysaccharide (8.5 to 6.7% packed cell volume, P not significant). Thus, cryptococcal virulence factors are not regulated coordinately. Moreover, although the phenoloxidase synthesizes an antioxidant, melanin, the enzyme is not induced by the oxidant, hydrogen peroxide, or by a combination of hydrogen peroxide and solubilized ferric ion. As cryptococcal melanin is cheaply made from exogenous catechols, perhaps C. neoformans does not need to regulate the phenoloxidase strongly but, rather, can afford to synthesize the phenoloxidase at a moderate rate whenever it finds its growth limited.