Are cytochrome b gene mutations the only cause of atovaquone resistance in Pneumocystis?
There is evidence that exposure of the opportunistic pathogen Pneumocystis to atovaquone enhances the development of resistance to the drug. Atovaquone is a structural analog of ubiquinone, which binds to the mitochondrial cytochrome bc(1) complex and inhibits electron transport. Like the parasites Plasmodium and Toxoplasma, atovaquone resistance can result from mutations in the cytochrome b gene of Pneumocystis. However, atovaquone resistance cannot be explained by cytochrome b gene mutations in all cases. The discovery that atovaquone also inhibits biosynthesis of ubiquinone in P. carinii may unfold other mechanisms by which drug resistance develops.
Kaneshiro
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Department of Biological Sciences, University of Cincinnati, Cincinnati, OH 45221, USA. Edna.Kaneshiro@uc.edu
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D053626:Atovaquone; D003573:Cytochrome b Group / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011010:Pneumocystis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D016720:Pneumocystis Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000382:microbiology*
D000935:Antifungal Agents; D003573:Cytochrome b Group; D009285:Naphthoquinones; D053626:Atovaquone