Inhibitory Effects of Fosmidomycin Against .

Front Cell Dev Biol

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.

Published: April 2020

, the main pathogen causing human babesiosis, has been reported to exhibit resistance to the traditional treatment of azithromycin + atovaquone and clindamycin + quinine, suggesting the necessity of developing new drugs. The methylerythritol 4-phosphate (MEP) pathway, a unique pathway in apicomplexan parasites, was shown to play a crucial function in the growth of . In the MEP pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is a rate-limiting enzyme and fosmidomycin (FSM) is a reported inhibitor for this enzyme. DXR has been shown as an antimalarial drug target, but no report is available on DXR (BmDXR). Here BmDXR was cloned, sequenced, analyzed by bioinformatics, and evaluated as a potential drug target for inhibiting the growth of . Drug assay was performed by adding different concentrations of FSM in culture. Rescue experiment was done by supplementing 200 μM isopentenyl pyrophosphate (IPP) or 5 μM geranylgeraniol (GG-ol) in the culture medium together with 5 μM FSM or 10 μM diminazene aceturate. The results indicated that FSM can inhibit the growth of in culture with an IC50 of 4.63 ± 0.12 μM, and growth can be restored by both IPP and GG-ol. Additionally, FSM is shown to inhibit the growth of parasites by suppressing the DXR activity, which agreed with the reported results of other apicomplexan parasites. Our results suggest the potential of DXR as a drug target for controlling and that FSM can inhibit the growth of .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198706PMC
http://dx.doi.org/10.3389/fcell.2020.00247DOI Listing

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