The erg11 gene codes for sterol 14-demethylase (14DM), a key enzyme in sterol biosynthesis and the target for triazole antimycotic drugs. Two sterol composition phenotypes have been described in patients with pneumonia caused by P. jirovecii; one phenotype has a much higher amount of lanosterol derivatives (C31 and C32 sterols) dominated by pneumocysterol. Most of the Pneumocystis-distinct sterols in this phenotype were those with a methyl group present at the C-14 position of the sterol nucleus suggesting that the P. jirovecii present might lack 14DM activity. To gain insight into whether the apparent lack of 14DM activity might be due to mutation of the erg11 gene, we have analyzed a 1,000-bp segment of this 1,800-bp gene in nine specimens of P. jirovecii (from the USA, Italy and Denmark). Thus far, two alleles of the erg11 gene have been observed: allele 1 with G at position 238 and allele 2 with A at this nucleotide position. All three specimens from Italy had allele 2, two of which were shown to contain high proportions of pneumocysterol. The other specimens analyzed had allele 1. The two alleles differ at a single site that is located in an apparent intron. Sequencing of the entire erg11 gene from these and additional samples is in progress.

Variation in the erg11 Gene from Pneumocystis jirovecii.

CONTINI, Carlo;
2010

Abstract

The erg11 gene codes for sterol 14-demethylase (14DM), a key enzyme in sterol biosynthesis and the target for triazole antimycotic drugs. Two sterol composition phenotypes have been described in patients with pneumonia caused by P. jirovecii; one phenotype has a much higher amount of lanosterol derivatives (C31 and C32 sterols) dominated by pneumocysterol. Most of the Pneumocystis-distinct sterols in this phenotype were those with a methyl group present at the C-14 position of the sterol nucleus suggesting that the P. jirovecii present might lack 14DM activity. To gain insight into whether the apparent lack of 14DM activity might be due to mutation of the erg11 gene, we have analyzed a 1,000-bp segment of this 1,800-bp gene in nine specimens of P. jirovecii (from the USA, Italy and Denmark). Thus far, two alleles of the erg11 gene have been observed: allele 1 with G at position 238 and allele 2 with A at this nucleotide position. All three specimens from Italy had allele 2, two of which were shown to contain high proportions of pneumocysterol. The other specimens analyzed had allele 1. The two alleles differ at a single site that is located in an apparent intron. Sequencing of the entire erg11 gene from these and additional samples is in progress.
2010
Pneumocystis jirovecii; Pneumocysterol; Drugs
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1407168
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