Enhancement of amphotericin B activity against Candida albicans by superoxide radical.
This study aimed to examine the involvement of oxidative damage in amphotericin B (AmB) activity against Candida albicans using the superoxide (O2-) generator paraquat (PQ). The effects of PQ on AmB activities against growth, viability, membrane permeability and respiration were examined in a wild-type parent strain (K) and a respiration-deficient mutant (KRD-19) since PQ-induced superoxide generation depends on respiration. In the parent strain, the minimal inhibitory concentration (MIC) of AmB, 0.25 microg/ml, tested with a liquid culture was lowered to 0.025 microg/ml by 1 mM PQ. Such a PQ-induced decrease in the MIC value of AmB was minimal in the mutant. Similar PQ-induced enhancement of AmB activity toward the parent strain was also observed with growth on an agar medium. In viability tests, when candidal cells were exposed to AmB (0.1 microg/ml) for I h, the lethality of AmB was enhanced by 1 mM PQ only in the parent strain. Exogenous superoxide dismutase and catalase failed to diminish the enhancing effect of PQ on the growth inhibitory activity of AmB in the parent strain, suggesting an interaction between superoxide and AmB in candidal cells. The enhancement of AmB activity by PQ, observed preferentially in the wild-type strain, can be explained by extensive superoxide generation depending on respiration. These results suggest that oxidative damage induced by superoxide is involved in AmB activity against C. albicans.
Department of Oral and Maxillofacial Surgery II, Nippon Dental University, Niigata 951-8580, Japan.
Yuichi
Y
Okamoto
Shigeji
S
Aoki
Izumi
I
Mataga
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D010269:Paraquat / Q000493:pharmacokinetics / Q000494:pharmacology*; D011048:Polarography; D013481:Superoxides / Q000493:pharmacokinetics / Q000494:pharmacology*
D000935:Antifungal Agents; D013481:Superoxides; D000666:Amphotericin B; D010269:Paraquat