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首页> 外文期刊>Journal of Parasitology >EFFECTS AND MECHANISMS OF ACTION OF IONOPHOROUS ANTIBIOTICS VALINOMYCIN AND SALINOMYCIN-Na ON BABESIA GIBSONI IN VITRO
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EFFECTS AND MECHANISMS OF ACTION OF IONOPHOROUS ANTIBIOTICS VALINOMYCIN AND SALINOMYCIN-Na ON BABESIA GIBSONI IN VITRO

机译：离子型抗菌剂缬霉素和沙林霉素钠对吉布森巴贝氏菌体外作用的作用机理

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摘要

Valinomycin and salinomycin-Na, 2 ionophorous antibiotics, exhibited in vitro antibabesial activities against Babesia gibsoni that infected normal canine erythrocytes containing low potassium (LK) and high sodium concentrations, i.e., LK erythrocytes, which completely lack Na,K-ATPase activity. The level of parasitemia of B. gibsoni was significantly decreased when the parasites were incubated in culture medium containing either 10−1 ng/ml valinomycin or 102 ng/ml salinomycin-Na for 24 hr. Four-hour incubation in the culture medium containing 5 µg/ml salinomycin-Na led to the destruction of most parasites. In contrast, when the parasites infected canine erythrocytes containing high potassium (HK) and low sodium concentrations, i.e., HK erythrocytes, the in vitro antibabesial activities of both ionophorous antibiotics seemed to be weakened, apparently due to the protection by the host cells. Therefore, differential influences of ionophorous antibiotics on LK and HK erythrocytes were observed. In LK erythrocytes, the intracellular concentrations of potassium, sodium, and adenosine triphosphate (ATP) were not modified, and hemolysis was not observed after incubation in the medium containing each ionophorous antibiotic. These results suggested that these ionophorous antibiotics did not affect cells without Na,K-ATPase, and directly affected B. gibsoni. In HK erythrocytes, the ionophorous antibiotics increased the intracellular sodium concentration, and decreased the intracellular potassium and ATP concentrations, causing obvious hemolysis. Additionally, the decrease of the intracellular ATP concentration and the hemolysis in HK erythrocytes caused by valinomycin disappeared when the activity of Na,K-ATPase was inhibited by ouabain. These results indicate that modification of the intracellular cation concentrations by the ionophorous antibiotics led to the activation of Na,K-ATPase and increased consumption of intracellular ATP, and that the depletion of intracellular ATP resulted in hemolysis in HK erythrocytes. Moreover, the antibabesial activity of valinomycin disappeared when B. gibsoni in LK erythrocytes were incubated in culture media containing high potassium concentrations. This showed that the intracellular cation concentration in the parasites was not modified in those media and would remain the same.
机译：Valinomycin和salinomycin-Na（2种离子载体抗生素）对吉贝斯贝氏菌表现出体外抗婴儿活性，感染了含有低钾（LK）和高钠浓度的正常犬红细胞，即完全缺乏Na，K-ATPase活性的LK红细胞。当将寄生虫在含有10 -1 ng / ml缬氨霉素或10 2 ng / ml盐霉素的培养基中孵育时，吉布森牛寄生虫的水平显着降低钠持续24小时。在含有5 µg / ml沙利霉素-Na的培养基中孵育4小时会破坏大多数寄生虫。相反，当寄生虫感染含有高钾（HK）和低钠浓度的犬红细胞，即HK红细胞时，两种离子载体抗生素的体外抗婴儿活性似乎减弱了，这显然是由于宿主细胞的保护。因此，观察到离子性抗生素对LK和HK红细胞的不同影响。在LK红细胞中，钾，钠和三磷酸腺苷（ATP）的细胞内浓度未改变，在含有每种离子载体抗生素的培养基中孵育后未观察到溶血。这些结果表明，这些离子载体的抗生素不影响没有Na，K-ATPase的细胞，而直接影响吉卜赛氏菌。在HK红细胞中，离子性抗生素会增加细胞内钠的浓度，并降低细胞内钾和ATP的浓度，导致明显的溶血。另外，当哇巴因抑制Na，K-ATPase的活性时，由缬霉素引起的细胞内ATP浓度的降低和HK红细胞的溶血现象消失。这些结果表明，通过离子载体抗生素对细胞内阳离子浓度的改变导致Na，K-ATP酶的活化和细胞内ATP的消耗增加，并且细胞内ATP的消耗导致HK红细胞溶血。此外，当在含有高钾浓度的培养基中孵育LK红细胞中的吉布森球菌时，缬霉素的抗婴儿活性消失。这表明在这些培养基中，寄生虫中细胞内阳离子的浓度没有改变，将保持不变。

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