Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure

Abstract

Theileriosis is an economically important haemoprotozoal disease with high morbidity and mortality in cattle. Buparvaquone is very effective in the treatment of Theileria infections in cattle. The present study reported an outbreak of bovine tropical theileriosis in Fars Province, southern Iran with buparvaquone treatment failure associated with mutations in drug-binding sites of its causative agent. The infected animals (n=8) exhibited poor condition, fever, anemia, rough coat and superficial lymph node enlargement. Both blood smears and lymph nodes punctures were positive and further molecular examination revealed that these animals were infected with Theileria annulata. Death occurred in seven of the eight infected animals in spite of the buparvaquone treatment. At molecular study, two types of important single-base mutations were observed in the cytochrome b gene of the parasite. These changes resulted in amino acid mutations in the parasite cytochrome b from serine (AGT) 109 to glycine (GGT) for the six dead cases and proline (CCT) 233 to serine (TCT) for one dead case within strongly Q(o) drug-binding sites. In contrast, neither of these mutations was found in the parasite cytochrome b for the buvarvaquone-treated animal. It seems that these mutation sites are associated with resistance to buparvaquone, a hydroxynaphthoquinone compound.