title: Effects and mechanisms of action of polyene macrolide antibiotic nystatin on Babesia gibsoni in vitro.
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 IC(50) 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.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. masayama@vetmed.hokudai.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tamura
authors.forename: Kensuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Noboru
authors.initials: N
authors.lastname: Sasaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.forename: Wickramasekara
authors.initials: W
authors.lastname: Rajapakshage
authors.forename: Bandula
authors.initials: B
authors.lastname: Kumara
authors.forename: Yu
authors.initials: Y
authors.lastname: Tamura
authors.forename: Sue Yee
authors.initials: SY
authors.lastname: Lim
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takiguchi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D001403:Babesia / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004285:Dogs; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects / Q000469:parasitology*; D020128:Inhibitory Concentration 50; D009504:Neutrophils / Q000187:drug effects; D009761:Nystatin / Q000494:pharmacology* / Q000633:toxicity; D011188:Potassium / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D009761:Nystatin; D011188:Potassium