Triclosan inhibits the growth of Neospora caninum in vitro and in vivo
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Neospora caninum is an apicomplexan parasite considered one of the main causes of abortion in cattle worldwide; thus, there is an urgent need to develop novel therapeutic agents to control the neosporosis. Enoyl acyl carrier protein reductase (ENR) is a key enzyme of the type II fatty acid synthesis pathway (FAS II), which is essential for apicomplexan parasite survival. The antimicrobial agent triclosan has been shown to be a very potent inhibitor of ENR. In this study, we identified an E. coli ENR-like protein in N. caninum. Multiple sequence alignment showed all the requisite features of ENR existed in this protein, so we named this protein NcENR. Swiss-Model analysis showed NcENR interacts with triclosan. We observed that ENR is localized in the apicoplast, a plastid-like organelle. Similar to the potent inhibition of triclosan on other apicomplexa parasites, this compound markedly inhibits the growth of N. caninum at low concentrations. Further research showed that triclosan attenuated the invasion ability and proliferation ability of N. caninum at low concentrations. The results from in vivo studies in the mouse showed that triclosan attenuated the virulence of N. caninum in mice mildly and reduced the parasite burden in the brain significantly. Taken together, triclosan inhibits the growth of N. caninum both in vitro and in vivo at low concentrations.
KeywordsNeospora Caninum Type II fatty acid synthesis pathway Enoyl acyl carrier protein reductase Triclosan
We thank Professor Xuenan Xuan (Obihiro University of Agriculture and Veterinary Medicine, Japan) for kindly providing the Nc-1 strain. We thank Jin Zhu (Therapeutic Goods Administration, Australia) for the helpful comments on the manuscript.
Availability of data and material
Data supporting the conclusions of this article are included within the article.
HZ and JL designed the study and analyzed the data. HZ, YF, and CSY carried out the experiments. JHX provided help for instrument operation. QL and JL contributed reagents and materials and offered advice during the research. All authors read and approved the final manuscript.
This study was supported by the National Key Basic Research Program (973 program) of China (No.2015CB150300) and the National Key Research and Development Program of China (2017YFD0501200).
Compliance with ethical standards
Ethics approval and consent to participate
The experimental procedures were performed strictly according to the recommendations of the Guide for the Care and Use of Laboratory Animals of the Ministry of Science and Technology of China and approved by the Institutional Animal Care and Use Committee of China Agricultural University (under the certificate of Beijing Laboratory Animal employee ID: CAU20161210-2).
Consent for publication
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
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