{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:38:31Z","timestamp":1784227111201,"version":"3.55.0"},"reference-count":69,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T00:00:00Z","timestamp":1368662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Blood\u2010stage <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>lasmodium<\/jats:italic> parasites cause morbidity and mortality from malaria. Parasite resistance to drugs makes development of new chemotherapies an urgency. Aminoacyl\u2010<jats:styled-content style=\"fixed-case\">tRNA<\/jats:styled-content> synthetases have been validated as antimalarial drug targets. We explored long\u2010term effects of borrelidin and mupirocin in lethal <jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>. yoelii<\/jats:italic> murine malaria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Long\u2010term (up to 340 days) immunological responses to borrelidin or mupirocin were measured after an initial 4 day suppressive test. Prophylaxis and cure were evaluated and the inhibitory effect on the parasites analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Borrelidin protected against lethal malaria at 0.25\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>. Antimalarial activity of borrelidin correlated with accumulation of trophozoites in peripheral blood. All infected mice treated with borrelidin survived and subsequently developed immunity protecting them from re\u2010infection on further challenges, 75 and 340 days after the initial infection. This long\u2010term immunity in borrelidin\u2010treated mice resulted in negligible parasitaemia after re\u2010infections and marked increases in total serum levels of antiparasite <jats:styled-content style=\"fixed-case\">IgGs<\/jats:styled-content> with augmented avidity. Long\u2010term memory <jats:styled-content style=\"fixed-case\">IgGs<\/jats:styled-content> mainly reacted against high and low molecular weight parasite antigens. Immunofluorescence microscopy showed that circulating <jats:styled-content style=\"fixed-case\">IgGs<\/jats:styled-content> bound predominantly to late intracellular stage parasites, mainly schizonts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Low borrelidin doses protected mice from lethal malaria infections and induced protective immune responses after treatment. Development of combination therapies with borrelidin and selective modifications of the borrelidin molecule to specifically inhibit plasmodial threonyl <jats:styled-content style=\"fixed-case\">tRNA<\/jats:styled-content> synthetase should improve therapeutic strategies for malaria.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12156","type":"journal-article","created":{"date-parts":[[2013,3,14]],"date-time":"2013-03-14T01:07:32Z","timestamp":1363223252000},"page":"645-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Insights into the preclinical treatment of blood\u2010stage malaria by the antibiotic borrelidin"],"prefix":"10.1111","volume":"169","author":[{"given":"IG","family":"Azc\u00e1rate","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology IV and Research Institute Hospital 12 de Octubre Universidad Complutense de Madrid  Madrid 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