DIFFERENT SUSCEPTIBILITY OF 3 CLINICALLY ISOLATED STRAINS OF CRYPTOCOCCUS-NEOFORMANS TO THE FUNGICIDAL EFFECTS OF REACTIVE NITROGEN AND OXYGEN INTERMEDIATES - POSSIBLE RELATIONSHIPS WITH VIRULENCE

We investigated the susceptibility of three clinically isolated strain s of Cryptococcus neoformans with different virulences to reactive nit rogen and oxygen intermediates (RNI and ROI, respectively), representi ng two important mediators of macrophage microbicidal activity. All mi ce infected with the highly virulent strain of C. neoformans, YC-11, d ied within 3 to 6 weeks because of rapid multiplication of the organis m in the lungs and dissemination to the brain, In contrast, a weakly v irulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infe cted animals during the period of observation (15 weeks). The virulenc e of the third strain, YC-5, was intermediate between the other two st rains. To examine the susceptibility of C. neoformans to the fungicida l effect of nitric oxide (NO) and superoxide anions (O-2(-)), the orga nisms were exposed to these oxidants, which were chemically generated in a cell-free system, Interestingly, the number of live YC-13 yeast c ells was markedly reduced after exposure to NO and O-2(-). In contrast , YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results dem onstrate that the resistance of C. neoformans to the fungicidal effect s of RNI and ROI is related to virulence, and suggest that the resista nce to nitrogen-and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.