Different Susceptibility of Three Clinically Isolated Strains of <i>Cryptococcus neoformans</i> to the Fungicidal Effects of Reactive Nitrogen and Oxygen Intermediates

J-STAGE
  • Xie Qifeng
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus
  • Kawakami Kazuyoshi
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus
  • Kudeken Norifumi
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus
  • Zhang Tiantuo
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus
  • Qureshi Mahboob Hossain
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus
  • Saito Atsushi
    The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus

抄録

We investigated the susceptibility of three clinically isolated strains of Cryptococcus neoformans with different virulences to reactive nitrogen and oxygen intermediates (RNI and ROI, respectively), representing two important mediators of macrophage microbicidal activity. All mice infected with the highly virulent strain of C. neoformans, YC-11, died within 3 to 6 weeks because of rapid multiplication of the organism in the lungs and dissemination to the brain. In contrast, a weakly virulent strain, YC-13, was almost completely eradicated from the lungs and did not disseminate to the brain, leading to survival of all infected animals during the period of observation (15 weeks). The virulence of the third strain, YC-5, was intermediate between the other two strains. To examine the susceptibility of C. neoformans to the fungicidal effect of nitric oxide (NO) and superoxide anions (O2-), the organisms were exposed to these oxidants, which were chemically generated in a cell-free system. Interestingly, the number of live YC-13 yeast cells was markedly reduced after exposure to NO and O2-. In contrast, YC-11 was almost completely resistant to the killing effect of these oxidants. YC-5 showed an intermediate susceptibility. Our results demonstrate that the resistance of C. neoformans to the fungicidal effects of RNI and ROI is related to virulence, and suggest that the resistance to nitrogen- and oxygen-derived oxidants may be one of the factors to determine the outcome of infection with C. neoformans.

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