title: Development of in vitro atovaquone-resistant Babesia gibsoni with a single-nucleotide polymorphism in cytb.
abstract: An atovaquone (ATV)-resistant Babesia gibsoni was developed by in vitro exposure of uncloned wild type (WT) B. gibsoni to 800 nM ATV for 6 days. Sequence analysis of mitochondrial genes showed a single-nucleotide polymorphism (SNP) at cytb nt363 (G to T) that resulted in the substitution of methionine with isoleucine (M121I), which is one of the SNPs reported in a previous in vivo study. 363T or 363G allele-specific real-time polymerase chain reaction (PCR) revealed that an M121I variant was present in over 99% of the ATV-resistant population. As neither ATV resistance nor gene polymorphisms appeared in the B. gibsoni WT sibling clones, the expression of ATV resistance in this study was suspected to be because of selective multiplication of the B. gibsoni M121I variant. This ATV-resistant B. gibsoni displayed the same sensitivity as the WT B. gibsoni against 5 other drugs, including diminazene aceturate, azithromycin, doxycycline, clindamycin, and proguanil. This is the first report on the in vitro establishment of an ATV-resistant B. gibsoni with gene polymorphisms.
authors: Department of Veterinary Internal Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
authors: Aiko
authors: A
authors: Iguchi
authors: Aya
authors: A
authors: Matsuu
authors: Hiromi
authors: H
authors: Ikadai
authors: Md Hasanuzzaman
authors: MH
authors: Talukder
authors: Yoshiaki
authors: Y
authors: Hikasa
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D053626:Atovaquone / Q000494:pharmacology*; D001403:Babesia / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D045303:Cytochromes b / Q000235:genetics* / Q000378:metabolism; D004285:Dogs; D004351:Drug Resistance / Q000235:genetics*; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D015800:Protozoan Proteins; D045303:Cytochromes b; D053626:Atovaquone