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Sterol Composition of Pneumocystis jirovecii with Blocked 14α‐Demethylase Activity
Author(s) -
GINER JOSÉLUIS,
ZHAO HUI,
AMIT ZUNIKA,
KANESHIRO EDNA S.
Publication year - 2004
Publication title -
journal of eukaryotic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 1066-5234
DOI - 10.1111/j.1550-7408.2004.tb00597.x
Subject(s) - sterol , ergosterol , biology , pneumocystis jirovecii , biochemistry , demethylase , methylation , cholesterol , phenotype , gene , immunology , human immunodeficiency virus (hiv) , epigenetics
Several drugs that interact with membrane sterols or inhibit their syntheses are effective in clearing a number of fungal infections. The AIDS‐associated lung infection caused by Pneumocystis jirovecii is not cleared by many of these therapies. Pneumocystis normally synthesizes distinct C 28 and C 29 24‐alkylsterols, but ergosterol, the major fungal sterol, is not among them. Two distinct sterol compositional phenotypes were previously observed in P. jirovecii . One was characterized by Δ 7 C 28 and C 29 24‐alkylsterols with only low proportions of higher molecular mass components. In contrast, the other type was dominated by high C 31 and C 32 24‐alkylsterols, especially pneumocysterol. In the present study, 28 molecular species were elucidated by nuclear magnetic resonance analysis of a human lung specimen containing P. jirovecii representing the latter sterol profile phenotype. Fifteen of the 28 had the methyl group at C‐14 of the sterol nucleus and these represented 96% of the total sterol mass in the specimen (excluding cholesterol). These results strongly suggest that sterol 14α‐demethylase was blocked in these organisms. Twenty‐four of the 28 were 24‐alkylsterols, indicating that methylation of the C‐24 position of the sterol side chain by S‐adenosyl‐L‐methionine:sterol C‐24 methyl transferase was fully functional.