Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors

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Abstract
Cryptococcus neoformansis a common cause of meningoencephalitis among AIDS patients. SeveralC. neoformansvirulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the corrrelation of the virulence of 18C. neoformansvar.grubiiisolates from AIDS patients with the expression of several well-described virulence factors. The LD50at 15 days after intracranial inoculation of ICR mice was 20 000 for 39 %. Higher cryptococcal concentrations in brains were noted for isolates with lower LD50(P=0.002). In survival studies, no immunocompetent BALB/c mice (nu/−) infected with 3×LD50of three virulent isolates (LD50=62, 99, 1280) survived beyond 23 days, whereas 100 %, 90 % and 90 % of mice infected with 20 000 c.f.u. of three hypovirulent isolates (LD50>20 000) survived for 60 days (Pnu/nu) mice, survival rates over 60 days were 100 %, 70 % and 50 %, respectively, for the hypovirulent isolates. Growth rate at 37 °C and capsule size within brains correlated with LD50by univariate (P=0.0001 and 0.028, respectively) and multivariate (P=0.017 and 0.016, respectively) analyses. There was no correlation between LD50and capsule sizein vitro, phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection byC. neoformansisolates of wide-ranging virulence, including isolates that are markedly hypovirulent. The virulence of a given isolate reflects a composite of factors rather than the contribution of a dominant factor. Growth at 37 °C and capsule sizein vivomake particularly important contributions.