Enhancement of amphotericin B activity against Candida albicans by superoxide radical
Enhancement of amphotericin B activity against Candida albicans by superoxide radical
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DOI：
10.1023/b:myco.0000038430.20669.80
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发表时间：
2004-07-01
期刊：
影响因子：
5.5
通讯作者：
Mataga, I
中科院分区：
文献类型：
--
作者：
Okamoto, Y;Aoki, S;Mataga, I
本研究的目的是研究氧化损伤的参与，阿替霉素B（AmB）的活性，使用超氧化物（O-2（-））发生器百草枯（PQ）对白色念珠菌。在野生型亲本菌株（K）和呼吸缺陷突变体（KRD-19）中检查了PQ对AmB活性对生长、活力、膜渗透性和呼吸的影响，因为PQ诱导的超氧化物生成依赖于呼吸。在亲本菌株中，用液体培养物测试的AmB的最小抑制浓度（MIC）（0.25 μ g/ml）通过1 mM PQ降低至0.025 μ g/ml。这种PQ诱导的AmB MIC值的降低在突变体中是最小的。在琼脂培养基上生长时，也观察到类似的PQ诱导的AmB活性向亲本菌株的增强。在生存力测试中，当念珠菌细胞暴露于AmB（0.1 μ g/ml）1小时，AmB的致死性增强1 mM PQ仅在亲本菌株。外源性超氧化物歧化酶和过氧化氢酶不能减弱PQ对AmB生长抑制活性的增强作用，表明超氧化物歧化酶和AmB在念珠菌细胞中存在相互作用。增强AmB活性的PQ，观察到优先在野生型菌株，可以解释为广泛的超氧化物生成依赖于呼吸。这些结果表明，超氧化物引起的氧化损伤参与了AmB抗C。白色念珠菌
This study aimed to examine the involvement of oxidative damage in amphotericin B (AmB) activity against Candida albicans using the superoxide (O-2(-)) 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 mug/ml, tested with a liquid culture was lowered to 0.025 mug/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 mug/ml) for 1 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.