Sequence polymorphisms in the Pneumocysits carinii cytochrome b gene and their association with atovaquone prophylaxis failure

Citation
Dj. Walker et al., Sequence polymorphisms in the Pneumocysits carinii cytochrome b gene and their association with atovaquone prophylaxis failure, J INFEC DIS, 178(6), 1998, pp. 1767-1775
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Immunology
Journal title
JOURNAL OF INFECTIOUS DISEASES
ISSN journal
0022-1899 → ACNP
Volume
178
Issue
6
Year of publication
1998
Pages
1767 - 1775
Database
ISI
SICI code
0022-1899(199812)178:6<1767:SPITPC>2.0.ZU;2-Q
Abstract
Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis cari nii, which probably acts by binding to cytochrome b and inhibiting electron transport, To assess the possibility that atovaquone resistance might be d eveloping, the genes for the cytochrome b from P. carinii sp, f. carinii an d P. carinii sp, f. hominis were partially sequenced. Eight of 10 patient i solates had cytochrome b genes with the same amino acid sequence, The P. ca rinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxi s failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Q(o)), These mutations are homologo us to mutations in other microorganisms that confer resistance to similar i nhibitors. Variations in the sequence of the I! carinii cytochrome b gene s uggest but do not prove the development of drug resistance.