Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites

AbouLaila, Mahmoud; Munkhjargal, Tserendorj; Sivakumar, Thillaiampalam; Ueno, Akira; Nakano, Yuki; Yokoyama, Masahiro; Yoshinari, Takeshi; Nagano, Daisuke; Kawasaki, Koji; Elbahy, Nasr; Yokoyama, Naoki; Igarashi, Ikuo

doi:10.1128/aac.05488-11

Cited by 61 publications

(61 citation statements)

References 70 publications

(89 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Munich strain of B. microti was maintained by passage in the blood of BALB/c mice (14). Sixty female BALB/c mice were purchased from CLEA Japan (Tokyo, Japan) and used for in vivo studies.…”

Section: Methodsmentioning

confidence: 99%

“…The effect of clofazimine on host erythrocytes was evaluated as described previously (14). Bovine and equine erythrocytes were incubated in the presence of 0.5, 1, 2, 5, 10, and 25 M clofazimine for 3 h at 37°C, and erythrocytes were then washed three times with drug-free medium and used for the cultivation of Babesia and Theileria parasites for 72 h. The untreated control cells were handled in the same manner as the pretreated cells.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro experiments were conducted as described previously (14). Briefly, 200 l of medium, medium with various concentrations of clofazimine based on the results of preliminary investigations, and medium with DMSO were added in triplicate in 96-well plates.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro cultures of B. bovis (Texas strain), B. bigemina (Argentina strain), and B. caballi and T. equi (both USDA strains) were used for the experiments (15). Parasites were grown in bovine or equine red blood cells (RBCs), using a continuous microaerophilous stationary-phase culture system (14). Medium 199 (Sigma-Aldrich) was used for B. bovis, B. bigemina, and T. equi, whereas RPMI 1640 (Sigma-Aldrich) was used for B. caballi.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Tuvshintulga

AbouLaila

Davaasuren

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC 50 s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 M, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine-and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti. On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofaziminetreated animals and in several tissues of clofazimine-and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Tuvshintulga

AbouLaila

Davaasuren

et al. 2016

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…29,30 N-Tris (hydroxymethyl) methyl-2-ainomethanesulfonic acid hemisodium salt (229 mg/mL) was added to bovine Babesia parasite cultures as a pH stabilizer (pH 7.2). 29,31,32 Culture plates for parasites were incubated in atmospheres of 5% CO 2 and 5% O 2 at 37 C. 29 Mice. The Munich strain of B. microti was maintained by passage in blood of BALB/c mice.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

Munkhjargal¹,

AbouLaila²,

Terkawi³

et al. 2012

The American Society of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Abstract. We evaluated the inhibitory effects of pepstatin A and mefloquine on the in vitro and in vivo growths of Babesia parasites. The in vitro growth of Babesia bovis, B. bigemina, B. caballi, and B. equi was significantly inhibited (P 0.05) by micromolar concentrations of pepstatin A (50% inhibitory concentrations = 38.5, 36.5, 17.6, and 18.1 μM, respectively) and mefloquine (50% inhibitory concentrations = 59.7, 56.7, 20.7, and 4 μM, respectively). Furthermore, both reagents either alone at a concentration of 5 mg/kg or in combinations (2.5/2.5 and 5/5 mg/kg) for 10 days significantly inhibited the in vivo growth of B. microti in mice. Mefloquine treatment was highly effective and the combination treatments were less effective than other treatments. Therefore, mefloquine may antagonize the actions of pepstatin A against babesiosis and aspartic proteases may play an important role in the asexual growth cycle of Babesia parasites.

show abstract

Discovery of the Mechanism of Action of Novel Compounds That Target Unicellular Eukaryotic Parasites

Begolo

Clayton

2016

Comprehensive Analysis of Parasite Biology: From Metabolism to Drug Discovery

View full text Add to dashboard Cite

Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites

Cited by 61 publications

References 70 publications

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Inhibitory Effects of Pepstatin A and Mefloquine on the Growth of Babesia Parasites

Discovery of the Mechanism of Action of Novel Compounds That Target Unicellular Eukaryotic Parasites

Contact Info

Product

Resources

About