Effects and Mechanisms of Action of Polyene Macrolide Antibiotic Nystatin on Babesia gibsoni In Vitro
Effects and Mechanisms of Action of Polyene Macrolide Antibiotic Nystatin on Babesia gibsoni In Vitro
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DOI：
10.1645/ge-2799.1
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
M. Yamasaki;N. Tamura;Kensuke Nakamura;N. Sasaki;Masahiro Murakami;Wickramasekara Rajapakshage;B. Kumara;Y. Tamura;S. Lim;H. Ohta;M. Takiguchi
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文献类型：
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作者：
M. Yamasaki;N. Tamura;Kensuke Nakamura;N. Sasaki;Masahiro Murakami;Wickramasekara Rajapakshage;B. Kumara;Y. Tamura;S. Lim;H. Ohta;M. Takiguchi
摘要制霉菌素是一种具有膜活性的多烯大环内酯类抗生素和离子通道载体。制霉菌素表现出抗吉氏巴氏巴氏杆菌感染含有低钾（LK）和高钠浓度的正常犬红细胞的体外活性，LK红细胞。制霉菌素对B.感染LK红细胞的gibsoni为31.96 μg/ml。B.将LK红细胞中的Gibsoni在含有高钾浓度（HK）的培养基中孵育。此外，当寄生虫窝藏在犬HK红细胞，其中含有高钾和低钠浓度的高Na-K-ATP酶活性的结果，制霉菌素的体外抗巴贝斯虫活性也消失，显然是由于HK红细胞的保护。这表明制霉菌素对B具有体外抗巴贝斯虫活性。Gibsoni通过其离子载体活性，与其他离子载体如缬氨霉素相同。随后，观察制霉菌素对宿主细胞的影响。制霉菌素不能改变LK或HK红细胞中钾、钠、三磷酸腺苷或葡萄糖的细胞内浓度，尽管它在HK红细胞中引起弱溶血。此外，制霉菌素不影响犬外周血多形核白细胞的存活。总之，制霉菌素破坏了B。Gibsoni通过离子转运活性，但在体外不影响犬红细胞或白细胞。
Abstract Nystatin is a membrane-active polyene macrolide antibiotic and a channel-forming ionophore. Nystatin exhibits in vitro activity against Babesia gibsoni infecting normal canine erythrocytes containing low potassium (LK) and high sodium concentrations, i.e., LK erythrocytes. The calculated IC50 value of nystatin against B. gibsoni infecting LK erythrocytes was 31.96 µg/ml. The anti-babesial activity of nystatin disappeared when B. gibsoni in LK erythrocytes were incubated in culture media containing high potassium concentrations (HK). Moreover, when the parasites were harbored in canine HK erythrocytes, which contained high potassium and low sodium concentrations as a result of high Na-K-ATPase activity, the in vitro anti-babesial activities of nystatin also disappeared, apparently due to protection by HK erythrocytes. This suggested that nystatin could show in vitro anti-babesial activity against B. gibsoni by its ionophorous activity, the same as other ionophores such as valinomycin. Subsequently, the effects of nystatin on the host cells were observed. Nystatin could not modify the intracellular concentrations of potassium, sodium, adenosine triphosphate, or glucose in either LK or HK erythrocytes, although it caused weak hemolysis in HK erythrocytes. In addition, nystatin did not affect the survival of canine peripheral polymorphonuclear leukocytes. In conclusion, nystatin destroyed B. gibsoni by ionophorous activity but did not affect either canine erythrocytes or leukocytes in vitro.