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

Academic Article

Abstract

  • Atovaquone (Mepron, 566c80) is an effective agent against Pneumocystis carinii, which probably acts by binding to cytochrome b and inhibiting electron transport. To assess the possibility that atovaquone resistance might be developing, the genes for the cytochrome b from P. carinii sp. f. carinii and P. carinii sp. f. hominis were partially sequenced. Eight of 10 patient isolates had cytochrome b genes with the same amino acid sequence. The P. carinii cytochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resulting in amino acid changes in one of the ubiquinone (coenzyme Q) binding sites (Q(o)). These mutations are homologous to mutations in other microorganisms that confer resistance to similar inhibitors. Variations in the sequence of the P. carinii cytochrome b gene suggest but do not prove the development of drug resistance.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Walker DJ; Wakefield AE; Dohn MN; Miller RF; Baughman RP; Hossler PA; Bartlett MS; Smith JW; Kazanjian P; Meshnick SR
  • Start Page

  • 1767
  • End Page

  • 1775
  • Volume

  • 178
  • Issue

  • 6