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A Targeted "Next-Generation" Sequencing-Informatic Approach to Define Genetic Diversity in Theileria orientalis Populations within Individual Cattle: Proof-of-Principle.

ABSTRACT: Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two of these genotypes (i.e., chitose and ikeda) are recognized as pathogenic in cattle, causing significant disease in countries of the Asia-Pacific region. However, the true extent of genetic variation and associated virulence/pathogenicity within this complex is unknown. Here, we undertook a proof-of-principle study of a small panel of genomic DNAs (n = 13) from blood samples originating from individual cattle known to harbor T. orientalis, in order to assess the performance of a targeted "next-generation" sequencing-informatic approach to identify genotypes. Five genotypes (chitose, ikeda, buffeli, type 4, and type 5) were defined; multiple genotypes were found within individual samples, with dominant and minor sequence types representing most genotypes. This study indicates that this sequencing-informatic workflow could be useful to assess the nature and extent of genetic variation within and among populations of T. orientalis on a large scale, and to potentially employ panels of distinct gene markers for expanded molecular epidemiological investigations of socioeconomically important protistan pathogens more generally.

SUBMITTER: Koehler AV

PROVIDER: S-EPMC7350381 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A Targeted "Next-Generation" Sequencing-Informatic Approach to Define Genetic Diversity in Theileria orientalis Populations within Individual Cattle: Proof-of-Principle.

Koehler Anson V AV Jabbar Abdul A Hall Ross S RS Gasser Robin B RB

Pathogens (Basel, Switzerland) 20200605 6

Oriental theileriosis is an economically important tickborne disease of bovines, caused by some members of the Theileria orientalis complex. Currently, 11 distinct operational taxonomic units (OTUs), or genotypes, are recognized based on their major piroplasm surface protein (MPSP) gene sequences. Two of these genotypes (i.e., chitose and ikeda) are recognized as pathogenic in cattle, causing significant disease in countries of the Asia-Pacific region. However, the tr ...[more]

PMID: 32517045

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Project description:IntroductionTheileria orientalis, an economically significant tick-borne hemoparasite, infects cattle globally. The T. orientalis Ikeda genotype, transmitted by Haemaphysalis longicornis ticks, is associated with clinical manifestations characterized by anemia, abortions, and mortality, although subclinical infections prevail. Despite the common occurrence of subclinical infections, therapeutic interventions targeting T. orientalis Ikeda in such cases are currently lacking, impeding effective parasite control measures. To address this critical knowledge gap, we assessed the efficacy of buparvaquone (BPQ) in eliminating the T. orientalis Ikeda, US isolate, in sub-clinically infected cattle.MethodsTwelve sub-clinically infected calves, identified by the presence of T. orientalis in peripheral blood alongside the absence of fever and anemia, were enrolled in the study. Six calves received two treatments of the BPQ label dose (2.5 mg/kg) at a 48-h interval, while additional three calves received the drug at a dosage of 6 mg/kg following the same regimen. Three untreated calves served as controls.Results and discussionEndpoint and quantitative PCR analyses revealed that BPQ exerted a transient effect on T. orientalis parasitemia. Parasites remained undetectable in peripheral blood until weeks 4 and 11 post-treatment in animals administered 2.5 mg/kg and 6 mg/kg of BPQ, respectively. Intriguingly, following recrudescence, administering 6 mg/kg to animals previously treated with 2.5 mg/kg did not result in a reduction in parasite load. Pharmacokinetic analysis data suggested that escalating the dosage led to a less than proportional increase in serum concentrations of BPQ. Moreover, a significant yet reversible decrease (p < 0.05) in blood urea nitrogen was observed in animals treated with the drug, irrespective of the dosage. Despite parasitemia relapse, animals treated with 6 mg/kg BPQ exhibited a noteworthy decrease (p < 0.05) in IgG levels specific to the T. orientalis major piroplasm surface protein compared to controls and animals treated with 2.5 mg/kg of the drug.ConclusionBPQ did not demonstrate efficacy in clearing subclinical T. orientalis Ikeda infection. Future investigations are warranted to explore innovative therapeutic modalities that, in synergy with vaccines and diagnostic assays, can facilitate the development of comprehensive programs aimed at controlling and eradicating this parasite.

Dataset Information

A Targeted "Next-Generation" Sequencing-Informatic Approach to Define Genetic Diversity in Theileria orientalis Populations within Individual Cattle: Proof-of-Principle.

Publications

A Targeted "Next-Generation" Sequencing-Informatic Approach to Define Genetic Diversity in <i>Theileria orientalis</i> Populations within Individual Cattle: Proof-of-Principle.

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