{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:39:26Z","timestamp":1787611166451,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Babesia bigemina<\/jats:italic> is a tick-borne apicomplexan hemoprotozoan responsible for bovine babesiosis. The current drugs used for bovine babesiosis treatment have several drawbacks, including toxicity, the lack of effectiveness to clear the parasite, and potential to develop resistance. Identifying compounds that target essential and unique parasite metabolic pathways is a rational approach toward finding alternative drug treatments. Based on the genome sequence and transcriptomics analysis, it can be inferred that anaerobic glycolysis is the dominant adenosine triphosphate (ATP) supply for <jats:italic>Babesia<\/jats:italic>, and lactate dehydrogenase (LDH) is one of the essential enzymes in this pathway. Furthermore, the <jats:italic>Babesia<\/jats:italic> LDH sequence is distinct from its bovine homologue and thus a potential chemotherapeutic target that would result in decreasing the ATP supply to the parasite but not to the host. Gossypol is a known efficient specific inhibitor of LDH in the <jats:italic>sensu stricto B. bovis<\/jats:italic> and the <jats:italic>sensu lato B. microti<\/jats:italic>, among other related parasites, but no such data are currently available in the <jats:italic>sensu stricto B. bigemina<\/jats:italic> parasites. Hereby, we show that the LDH amino acid sequence is highly conserved among <jats:italic>sensu stricto<\/jats:italic> but not in <jats:italic>sensu lato Babesia<\/jats:italic> spp. A predictive structural analysis of <jats:italic>B. bigemina<\/jats:italic> LDH showed the conservation of the key amino acids involved in the binding to gossypol compared to <jats:italic>B. bovis<\/jats:italic>. Gossypol has a significant (P &amp;lt; 0.0001) inhibitory effect on the <jats:italic>in vitro<\/jats:italic> growth of <jats:italic>B. bigemina<\/jats:italic>, with IC<jats:sub>50<\/jats:sub> of 43.97 mM after 72 h of treatment. The maximum IC (IC<jats:sub>98<\/jats:sub>) was observed at 60 mM gossypol. However, a significant effect on the viability of cattle PBMC was observed when the cells were cultured with 60 mM (IC<jats:sub>98<\/jats:sub>) gossypol compared with DMSO-exposed control cells. Interestingly, <jats:italic>B. bigemina<\/jats:italic> cultured at 3% oxygen expresses significantly higher levels of LDH and is more resistant to gossypol than the parasites maintained at ambient conditions containing ~20% oxygen. Altogether, the results suggest the potential of gossypol as an effective drug against <jats:italic>B. bigemina<\/jats:italic> infection, but the risk of host toxicity at therapeutic doses should be further evaluated in <jats:italic>in vivo<\/jats:italic> studies.<\/jats:p>","DOI":"10.3389\/fcimb.2022.870852","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T05:46:15Z","timestamp":1650347175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Lactate Dehydrogenase as a Potential Therapeutic Drug Target to Control Babesia bigemina"],"prefix":"10.3389","volume":"12","author":[{"given":"Lan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginaldo G.","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Laughery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Suarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S247","DOI":"10.1017\/s0031182004005190","article-title":"Babesiosis of Cattle","author":"Bock","year":"2004","journal-title":"Parasitology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.molbiopara.2004.03.009","article-title":"Identification of Babesia Bovis L-Lactate Dehydrogenase as a Potential Chemotherapeutical Target Against Bovine Babesiosis","volume":"136","author":"Bork","year":"2004","journal-title":"Mol. 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