Qasim Ali , Osama Zahid , Moez Mhadhbi , Ben Jones , Mohamed Aziz Darghouth , George Raynes , Kiran Afshan , Richard Birtles , Neil D. Sargison , Martha Betson , Umer Chaudhry
{"title":"牛环芽孢杆菌细胞色素b位点的遗传特征及其对布帕伐酮抗性的影响","authors":"Qasim Ali , Osama Zahid , Moez Mhadhbi , Ben Jones , Mohamed Aziz Darghouth , George Raynes , Kiran Afshan , Richard Birtles , Neil D. Sargison , Martha Betson , Umer Chaudhry","doi":"10.1016/j.ijpddr.2022.08.004","DOIUrl":null,"url":null,"abstract":"<div><p>Control of tropical theileriosis, caused by the apicomplexan <em>Theileria annulata</em>, depends on the use of a single drug, buparvaquone, the efficacy of which is compromised by the emergence of resistance. The present study was undertaken to improve understanding of the role of mutations conferring buparvaquone resistance in <em>T. annulata</em>, and the effects of selection pressures on their emergence and spread. First, we investigated genetic characteristics of the cytochrome b locus associated with buparvaquone resistance in 10 susceptible and 7 resistant <em>T. annulata</em> isolates. The 129G (GGC) mutation was found in the Q<sub>01</sub> binding pocket and 253S (TCT) and 262S (TCA) mutations were identified within the Q<sub>02</sub> binding pocket. Next, we examined field isolates and identified cytochrome b mutations 129G (GGC), 253S (TCT) and 262S (TCA) in 21/75 buffalo-derived and 19/119 cattle-derived <em>T. annulata</em> isolates, providing evidence of positive selection pressure. Both hard and soft selective sweeps were identified, with striking differences between isolates. For example, 19 buffalo-derived and 7 cattle-derived isolates contained 129G (GGC) and 253S (TCT) resistance haplotypes at a high frequency, implying the emergence of resistance by a single mutation. Two buffalo-derived and 12 cattle-derived isolates contained equally high frequencies of 129G (GGC), 253S (TCT), 129G (GGC)/253S (TCT) and 262S (TCA) resistance haplotypes, implying the emergence of resistance by pre-existing or recurrent mutations. Phylogenetic analysis further revealed that 9 and 21 unique haplotypes in buffalo and cattle-derived isolates were present in a single lineage, suggesting a single origin. We propose that animal migration between farms is an important factor in the spread of buparvaquone resistance in endemic regions of Pakistan. The overall outcomes will be useful in understanding how drug resistance emerges and spreads, and this information will help design strategies to optimise the use and lifespan of the single most drug use to control tropical theileriosis.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"20 ","pages":"Pages 65-75"},"PeriodicalIF":4.1000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/2c/main.PMC9529669.pdf","citationCount":"0","resultStr":"{\"title\":\"Genetic characterisation of the Theileria annulata cytochrome b locus and its impact on buparvaquone resistance in bovine\",\"authors\":\"Qasim Ali , Osama Zahid , Moez Mhadhbi , Ben Jones , Mohamed Aziz Darghouth , George Raynes , Kiran Afshan , Richard Birtles , Neil D. Sargison , Martha Betson , Umer Chaudhry\",\"doi\":\"10.1016/j.ijpddr.2022.08.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Control of tropical theileriosis, caused by the apicomplexan <em>Theileria annulata</em>, depends on the use of a single drug, buparvaquone, the efficacy of which is compromised by the emergence of resistance. The present study was undertaken to improve understanding of the role of mutations conferring buparvaquone resistance in <em>T. annulata</em>, and the effects of selection pressures on their emergence and spread. First, we investigated genetic characteristics of the cytochrome b locus associated with buparvaquone resistance in 10 susceptible and 7 resistant <em>T. annulata</em> isolates. The 129G (GGC) mutation was found in the Q<sub>01</sub> binding pocket and 253S (TCT) and 262S (TCA) mutations were identified within the Q<sub>02</sub> binding pocket. Next, we examined field isolates and identified cytochrome b mutations 129G (GGC), 253S (TCT) and 262S (TCA) in 21/75 buffalo-derived and 19/119 cattle-derived <em>T. annulata</em> isolates, providing evidence of positive selection pressure. Both hard and soft selective sweeps were identified, with striking differences between isolates. For example, 19 buffalo-derived and 7 cattle-derived isolates contained 129G (GGC) and 253S (TCT) resistance haplotypes at a high frequency, implying the emergence of resistance by a single mutation. Two buffalo-derived and 12 cattle-derived isolates contained equally high frequencies of 129G (GGC), 253S (TCT), 129G (GGC)/253S (TCT) and 262S (TCA) resistance haplotypes, implying the emergence of resistance by pre-existing or recurrent mutations. Phylogenetic analysis further revealed that 9 and 21 unique haplotypes in buffalo and cattle-derived isolates were present in a single lineage, suggesting a single origin. We propose that animal migration between farms is an important factor in the spread of buparvaquone resistance in endemic regions of Pakistan. The overall outcomes will be useful in understanding how drug resistance emerges and spreads, and this information will help design strategies to optimise the use and lifespan of the single most drug use to control tropical theileriosis.</p></div>\",\"PeriodicalId\":13775,\"journal\":{\"name\":\"International Journal for Parasitology: Drugs and Drug Resistance\",\"volume\":\"20 \",\"pages\":\"Pages 65-75\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/2c/main.PMC9529669.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal for Parasitology: Drugs and Drug Resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2211320722000215\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal for Parasitology: Drugs and Drug Resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2211320722000215","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Genetic characterisation of the Theileria annulata cytochrome b locus and its impact on buparvaquone resistance in bovine
Control of tropical theileriosis, caused by the apicomplexan Theileria annulata, depends on the use of a single drug, buparvaquone, the efficacy of which is compromised by the emergence of resistance. The present study was undertaken to improve understanding of the role of mutations conferring buparvaquone resistance in T. annulata, and the effects of selection pressures on their emergence and spread. First, we investigated genetic characteristics of the cytochrome b locus associated with buparvaquone resistance in 10 susceptible and 7 resistant T. annulata isolates. The 129G (GGC) mutation was found in the Q01 binding pocket and 253S (TCT) and 262S (TCA) mutations were identified within the Q02 binding pocket. Next, we examined field isolates and identified cytochrome b mutations 129G (GGC), 253S (TCT) and 262S (TCA) in 21/75 buffalo-derived and 19/119 cattle-derived T. annulata isolates, providing evidence of positive selection pressure. Both hard and soft selective sweeps were identified, with striking differences between isolates. For example, 19 buffalo-derived and 7 cattle-derived isolates contained 129G (GGC) and 253S (TCT) resistance haplotypes at a high frequency, implying the emergence of resistance by a single mutation. Two buffalo-derived and 12 cattle-derived isolates contained equally high frequencies of 129G (GGC), 253S (TCT), 129G (GGC)/253S (TCT) and 262S (TCA) resistance haplotypes, implying the emergence of resistance by pre-existing or recurrent mutations. Phylogenetic analysis further revealed that 9 and 21 unique haplotypes in buffalo and cattle-derived isolates were present in a single lineage, suggesting a single origin. We propose that animal migration between farms is an important factor in the spread of buparvaquone resistance in endemic regions of Pakistan. The overall outcomes will be useful in understanding how drug resistance emerges and spreads, and this information will help design strategies to optimise the use and lifespan of the single most drug use to control tropical theileriosis.
期刊介绍：
The International Journal for Parasitology – Drugs and Drug Resistance is one of a series of specialist, open access journals launched by the International Journal for Parasitology. It publishes the results of original research in the area of anti-parasite drug identification, development and evaluation, and parasite drug resistance. The journal also covers research into natural products as anti-parasitic agents, and bioactive parasite products. Studies can be aimed at unicellular or multicellular parasites of human or veterinary importance.
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