Publicação
A metabolite-based resistance mechanism against malaria
| dc.contributor.author | Figueiredo, Ana M. | |
| dc.contributor.author | Rastogi, Sónia Trikha | |
| dc.contributor.author | Ramos, Susana | |
| dc.contributor.author | Nogueira, Fátima | |
| dc.contributor.author | Villiers, Katherine De | |
| dc.contributor.author | Sousa, António G. Gonçalves de | |
| dc.contributor.author | Votborg-Novel, Lasse | |
| dc.contributor.author | Wedel, Cäcilie von | |
| dc.contributor.author | Tober-Lau, Pinkus | |
| dc.contributor.author | Jentho, Elisa | |
| dc.contributor.author | Pagnotta, Sara | |
| dc.contributor.author | Mesquita, Miguel | |
| dc.contributor.author | Cardoso, Sílvia | |
| dc.contributor.author | Bortolussi, Giulia | |
| dc.contributor.author | Muro, Andrés F. | |
| dc.contributor.author | Tranfield, Erin M. | |
| dc.contributor.author | Thibaud, Jessica | |
| dc.contributor.author | Duarte, Denise | |
| dc.contributor.author | Sousa, Ana Laura | |
| dc.contributor.author | Pinto, Sandra N. | |
| dc.contributor.author | Kitoko, Jamil | |
| dc.contributor.author | Mombo-Ngoma, Ghyslain | |
| dc.contributor.author | Mischlinger, Johannes | |
| dc.contributor.author | Junttila, Sini | |
| dc.contributor.author | Alenquer, Marta | |
| dc.contributor.author | Amorim, Maria João | |
| dc.contributor.author | Vasavda, Chirag | |
| dc.contributor.author | Bosma, Piter J. | |
| dc.contributor.author | Violante, Sara | |
| dc.contributor.author | Drotleff, Bernhard | |
| dc.contributor.author | Paixão, Tiago | |
| dc.contributor.author | Portugal, Silvia | |
| dc.contributor.author | Kurth, Florian | |
| dc.contributor.author | Elo, Laura L. | |
| dc.contributor.author | Paul, Bindu D. | |
| dc.contributor.author | Martins, Rui | |
| dc.contributor.author | Soares, Miguel P. | |
| dc.date.accessioned | 2026-08-03T15:25:50Z | |
| dc.date.available | 2026-08-03T15:25:50Z | |
| dc.date.issued | 2025-02-26 | |
| dc.description.abstract | Whether jaundice, a common presentation of Plasmodium (P.) falciparum malaria (1-3) arising from the accumulation of circulating bilirubin, represents an adaptive or maladaptive response to Plasmodium spp. infection is not understood (1-3). We found that asymptomatic P. falciparum infection was associated with a >10-fold higher ratio of unconjugated bilirubin over parasite burden, compared to symptomatic malaria. Genetic suppression of bilirubin synthesis by biliverdin reductase A (BVRA) (4) increased parasite virulence and malaria mortality in mice. Accumulation of unconjugated bilirubin in plasma, via genetic inhibition of hepatic conjugation by UDP glucuronosyltransferase family 1 member A1 (UGT1A1) (5), was protective against malaria in mice. Unconjugated bilirubin inhibited P. falciparum proliferation in red blood cells (RBC) via a mechanism that suppressed mitochondrial pyrimidine synthesis. Moreover, unconjugated bilirubin inhibited hemozoin (Hz) crystallization and compromised the parasite’s food vacuole. In conclusion, jaundice represents a metabolic response to Plasmodium spp. infection that limits malaria severity. | eng |
| dc.identifier.doi | 10.1101/2025.02.20.639306 | |
| dc.identifier.other | dc80a79b-3eaa-446d-a328-9205376bb6af | |
| dc.identifier.uri | http://hdl.handle.net/10400.14/59010 | |
| dc.language.iso | eng | |
| dc.publisher | bioRxiv | |
| dc.rights.uri | N/A | |
| dc.title | A metabolite-based resistance mechanism against malaria | |
| dc.type | preprint | |
| dspace.entity.type | Publication | |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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