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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. Microbiology 2006 Aug;152(Pt 8):2247-55

Date

07/20/2006

Pubmed ID

16849791

DOI

10.1099/mic.0.28798-0

Scopus ID

2-s2.0-33747149174   22 Citations

Abstract

Cryptococcus neoformans is a common cause of meningoencephalitis among AIDS patients. Several C. neoformans virulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the correlation of the virulence of 18 C. neoformans var. grubii isolates from AIDS patients with the expression of several well-described virulence factors. The LD50 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 LD50 (P = 0.002). In survival studies, no immunocompetent BALB/c mice (nu/-) infected with 3 x LD50 of 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 (P < 0.0001). Even among BALB/c nude (nu/nu) mice, survival rates over 60 days were 100 %, 70 % and 50 %, respectively, for the hypovirulent isolates. Growth rate at 37 degrees C and capsule size within brains correlated with LD50 by univariate (P = 0.0001 and 0.028, respectively) and multivariate (P = 0.017 and 0.016, respectively) analyses. There was no correlation between LD50 and capsule size in vitro, phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection by C. neoformans 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 degrees C and capsule size in vivo make particularly important contributions.

Author List

Clancy CJ, Nguyen MH, Alandoerffer R, Cheng S, Iczkowski K, Richardson M, Graybill JR

Author

Kenneth A. Iczkowski MD Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

AIDS-Related Opportunistic Infections
Animals
Cryptococcosis
Cryptococcus neoformans
Humans
Lung
Male
Meningoencephalitis
Mice
Mice, Inbred BALB C
Mice, Inbred ICR
Virulence
Virulence Factors
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc