DISCORDANT REGULATION OF PHENOLOXIDASE AND CAPSULAR POLYSACCHARIDE INCRYPTOCOCCUS-NEOFORMANS

We examined the regulation of two fungal virulence factors, phenoloxid ase and capsular polysaccharide, in an ex-type strain of the fungal pa thogen, Cryptococcus neoformans. Both were made during the stationary phase of cultural growth. Exogenous iron increased phenoloxidase activ ity 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 volu me, P < 0.01). A temperature shift from 25 to 37 degrees C decreased p henoloxidase 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 regu lated coordinately. Moreover, although the phenoloxidase synthesizes a n antioxidant, melanin, the enzyme is not induced by the oxidant, hydr ogen peroxide, or by a combination of hydrogen peroxide and solubilize d ferric ion. As cryptococcal melanin is cheaply made from exogenous c atechols, perhaps C. neoformans does not need to regulate the phenolox idase strongly but, rather, can afford to synthesize the phenoloxidase at a moderate rate whenever it finds its growth limited.