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

Abstract

is a common cause of meningoencephalitis among AIDS patients. Several virulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the corrrelation of the virulence of 18 var. isolates from AIDS patients with the expression of several well-described virulence factors. The LD at 15 days after intracranial inoculation of ICR mice was <100 c.f.u. for 22 % of isolates, 100–1000 for 28 %, 1000–10 000 for 11 % and >20 000 for 39 %. Higher cryptococcal concentrations in brains were noted for isolates with lower LD (=0.002). In survival studies, no immunocompetent BALB/c mice (/−) infected with 3×LD of three virulent isolates (LD=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 (LD>20 000) survived for 60 days (<0.0001). Even among BALB/c nude (/) 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 LD by univariate (=0.0001 and 0.028, respectively) and multivariate (=0.017 and 0.016, respectively) analyses. There was no correlation between LD and capsule size , phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection by isolates 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 size make particularly important contributions.

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2006-08-01
2024-03-29
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