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Targeting liver stage malaria with metformin

2019Artigo científico Acesso aberto
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dc.contributor.authorVera, Iset
dc.contributor.authorRuivo, Margarida
dc.contributor.authorLEMOS ROCHA, Leonardo Filipe
dc.contributor.authorMarques, Sofia
dc.contributor.authorBhatia, Sangeeta N.
dc.contributor.authorMota, Maria M.
dc.contributor.authorMancio-Silva, Liliana
dc.date.accessioned2021-12-10T14:03:22Z
dc.date.available2021-12-10T14:03:22Z
dc.date.issued2019
dc.descriptionCopyright: © 2019, American Society for Clinical Investigationpt_PT
dc.description.abstractDespite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise in antiparasite drug resistance. Alternative approaches are urgently needed. Repurposing of available, approved drugs with distinct modes of action are being considered as viable and immediate adjuncts to standard antimicrobial treatment. Such strategies may be well suited to the obligatory and clinically silent first phase of Plasmodium infection, where massive parasite replication occurs within hepatocytes in the liver. Here, we report that the widely used antidiabetic drug, metformin, impairs parasite liver stage development of both rodent-infecting Plasmodium berghei and human-infecting P. falciparum parasites. Prophylactic treatment with metformin curtails parasite intracellular growth in vitro. An additional effect was observed in mice with a decrease in the numbers of infected hepatocytes. Moreover, metformin provided in combination with conventional liver- or blood-acting antimalarial drugs further reduced the total burden of P. berghei infection and substantially lessened disease severity in mice. Together, our findings indicate that repurposing of metformin in a prophylactic regimen could be considered for malaria chemoprevention.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (Portugal) PTDC/SAU-MET/118199/2010 to LMS and European Research Council Proof of Concept Grant to MMM (ERC-2015-PoC-DL3–713691-REUSE4MALARIA).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJCI Insight. 2019 Dec 19;4(24):e127441pt_PT
dc.identifier.doi10.1172/jci.insight.127441pt_PT
dc.identifier.eissn2379-3708
dc.identifier.urihttp://hdl.handle.net/10451/50330
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Clinical Investigationpt_PT
dc.relationERC-2015-PoC-DL3–713691-REUSE4MALARIApt_PT
dc.relationMechanisms of nutrient-sensing by the malaria parasite
dc.relation.publisherversionhttps://insight.jci.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectDrug therapypt_PT
dc.subjectInfectious diseasept_PT
dc.subjectMalariapt_PT
dc.subjectMicrobiologypt_PT
dc.subjectParasitologypt_PT
dc.titleTargeting liver stage malaria with metforminpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMechanisms of nutrient-sensing by the malaria parasite
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-MET%2F118199%2F2010/PT
oaire.citation.issue24pt_PT
oaire.citation.titleJCI Insightpt_PT
oaire.citation.volume4pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameVera
person.familyNameRuivo
person.familyNameLEMOS ROCHA
person.familyNameMarques
person.familyNameMota
person.familyNameMancio-Silva
person.givenNameIset
person.givenNameMargarida
person.givenNameLeonardo Filipe
person.givenNameSofia
person.givenNameMaria Manuel
person.givenNameLiliana
person.identifier864685
person.identifier.ciencia-id201E-7D43-52AA
person.identifier.ciencia-id4217-0969-297E
person.identifier.orcid0000-0003-4835-9437
person.identifier.orcid0000-0001-8667-9250
person.identifier.orcid0000-0002-8731-6440
person.identifier.orcid0000-0003-1467-1529
person.identifier.orcid0000-0002-2858-1041
person.identifier.orcid0000-0002-5585-018X
person.identifier.ridF-9905-2013
person.identifier.scopus-author-id16308336900
person.identifier.scopus-author-id7004641665
person.identifier.scopus-author-id7102709816
person.identifier.scopus-author-id8866484900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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