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
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.