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Slow growing behavior in African trypanosomes during adipose tissue colonization

2022Journal article Open access
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dc.contributor.authorTrindade, Sandra
dc.contributor.authorDe Niz, Mariana
dc.contributor.authorSequeira, Mariana
dc.contributor.authorRebelo, Tiago
dc.contributor.authorBento, Fabio
dc.contributor.authorDejung, Mario
dc.contributor.authorNarciso, Marta Valido
dc.contributor.authorEscobar, Lara
dc.contributor.authorFerreira, João
dc.contributor.authorButter, Falk
dc.contributor.authorBringaud, Frédéric
dc.contributor.authorGjini, Erida
dc.contributor.authorFigueiredo, Luisa M.
dc.date.accessioned2023-02-15T14:43:49Z
dc.date.available2023-02-15T14:43:49Z
dc.date.issued2022
dc.description© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.pt_PT
dc.description.abstractWhen Trypanosoma brucei parasites, the causative agent of sleeping sickness, colonize the adipose tissue, they rewire gene expression. Whether this adaptation affects population behavior and disease treatment remained unknown. By using a mathematical model, we estimate that the population of adipose tissue forms (ATFs) proliferates slower than blood parasites. Analysis of the ATFs proteome, measurement of protein synthesis and proliferation rates confirm that the ATFs divide on average every 12 h, instead of 6 h in the blood. Importantly, the population of ATFs is heterogeneous with parasites doubling times ranging between 5 h and 35 h. Slow-proliferating parasites remain capable of reverting to the fast proliferation profile in blood conditions. Intravital imaging shows that ATFs are refractory to drug treatment. We propose that in adipose tissue, a subpopulation of T. brucei parasites acquire a slow growing behavior, which contributes to disease chronicity and treatment failure.pt_PT
dc.description.sponsorshipThe project leading to this application has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 771714). This work was also supported by IC&DT Programa de Actividades Conjuntas – ref. 016417 “Oneida”, PTDC/BIMMET/4471/2014 and PTDC/CVT-CVT/29161/2017 (FCT). SFRH/BPD/89833/2012 and DL 57/2016/CP1451/CT0019 (FCT) to S.T, LT000047/2019-L (HFSP) and ALTF 1048-2016 (EMBO) to M.D.N, MSCA ITN Cell2Cell fellowship to L.LE and CEECIND/03322/2018 (FCT) to L.M.F. FBr is supported by the Agence National de Recherche (ANR, grant number ANR19-CE15-0004-01: ADIPOTRYP), the Fondation pour le Recherche Médicale (FRM, grant n°EQU201903007845: “Equipe FRM”) and the Laboratoire d’Excellence (grant number ANR-11-LABX-0024:ParaFrap).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNat Commun. 2022 Dec 8;13(1):7548pt_PT
dc.identifier.doi10.1038/s41467-022-34622-wpt_PT
dc.identifier.eissn2041-1723
dc.identifier.urihttp://hdl.handle.net/10451/56325
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relationPTDC/BIMMET/4471/2014pt_PT
dc.relationNot available
dc.relationNot Available
dc.relationALTF 1048-2016pt_PT
dc.relationNot Available
dc.relation.publisherversionhttps://www.nature.com/ncomms/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleSlow growing behavior in African trypanosomes during adipose tissue colonizationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNot available
oaire.awardTitleNot Available
oaire.awardTitleNot Available
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FCVT-CVT%2F29161%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F89833%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/DL 57%2F2016/DL 57%2F2016%2FCP1451%2FCT0019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2018/CEECIND%2F03322%2F2018%2FCP1543%2FCT0009/PT
oaire.citation.issue1pt_PT
oaire.citation.titleNature Communicationspt_PT
oaire.citation.volume13pt_PT
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamOE
oaire.fundingStreamDL 57/2016
oaire.fundingStreamCEEC IND 2018
person.familyNameTrindade
person.familyNameDe Niz
person.familyNameSequeira
person.familyNameRebelo
person.familyNameBento
person.familyNameValido Narciso
person.familyNameEscobar
person.familyNameFigueiredo
person.givenNameSandra
person.givenNameMariana
person.givenNameMariana
person.givenNameTiago
person.givenNameFabio
person.givenNameMarta
person.givenNameLara
person.givenNameLuisa M
person.identifier1058659
person.identifier.ciencia-id7015-C251-4765
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person.identifier.orcid0000-0003-1486-5403
person.identifier.orcid0000-0001-6461-961X
person.identifier.orcid0000-0002-0786-3912
person.identifier.orcid0000-0001-8605-2212
person.identifier.orcid0000-0002-0196-8764
person.identifier.orcid0000-0002-5752-6586
person.identifier.scopus-author-id35077932900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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