[Effects of combined addition of atovaquone and lithium on the in vitro cell growth of the pathogenic yeast Candida albicans].
Atovaquone, an analog of ubiquinone, binds tightly to the ubiquinol oxidation site (Qo site) of parasite cytochrome bc(1) complex to inhibit electron transport at concentrations far lower than those at which the mammalian system is affected. The mode of action is thought similar to that of myxothiazol. To treat Pneumocystis jirovecii and Plasmodium falciparum infections, atovaquone has been used worldwide whereas it is unapproved in Japan. Since the pathogenic Candida species fungi seem resistant to atovaquone, this drug is not clinically available for candidosis, particularly deep mycosis. We examined the effects of atovaquone on cellular respiration and in vitro growth of C. albicans to explore a new therapeutic possibility for fungal infections. Atovaquone strongly inhibited glucose-dependent cellular respiration similarly to antimycin A, stigmatellin, and myxothiazol, specific bc(1) complex inhibitors. However, atovaquone suppressed glucose-dependent cell growth to a much lesser extent versus the comparator agents. When added alone, lithium exerted slight growth inhibition. The combined addition of lithium with atovaquone showed a significant increase in inhibition of growth. Although the way lithium acts synergistically with atovaquone remains to be elucidated, our results suggest a new therapeutic possibility of this combination for the treatment of candidosis.
Minagawa
Nobuko
N
Department of Biochemistry, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. minagawa@nupals.ac.jp
Uehara
Mariko
M
Seki
Shiori
S
Nitta
Ayumi
A
Kogawara
Kento
K
D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053626:Atovaquone / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000254:growth & development* / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy; D004338:Drug Combinations; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D004338:Drug Combinations; D018020:Lithium Compounds; D053626:Atovaquone