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Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway

2023Journal article Open access
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dc.contributor.authorJia, Lei-Jie
dc.contributor.authorRafiq, Muhammad
dc.contributor.authorRadosa, Lukáš
dc.contributor.authorHortschansky, Peter
dc.contributor.authorCunha, Cristina
dc.contributor.authorCseresnyés, Zoltán
dc.contributor.authorKrüger, Thomas
dc.contributor.authorSchmidt, Franziska
dc.contributor.authorHeinekamp, Thorsten
dc.contributor.authorStraßburger, Maria
dc.contributor.authorLöffler, Bettina
dc.contributor.authorDoenst, Torsten
dc.contributor.authorLacerda, João
dc.contributor.authorCampos, António
dc.contributor.authorFigge, Marc Thilo
dc.contributor.authorCarvalho, Agostinho
dc.contributor.authorKniemeyer, Olaf
dc.contributor.authorBrakhage, Axel A.
dc.date.accessioned2023-03-14T14:09:14Z
dc.date.available2023-03-14T14:09:14Z
dc.date.issued2023
dc.description© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).pt_PT
dc.description.abstractThe decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion.pt_PT
dc.description.sponsorshipThis work was funded by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence Balance of the Microverse (Project-ID 390713860, Gepris 2051), the DFG-ANR project “AfuInf (316898429),” DFG CRC/Transregio 124 “FungiNet” (A1, Z2; 210879364), DFG CRC 1278 “PolyTarget” (Z01; 316213987), Leibniz project (K217/2016), Fundação para a Ciência e a Tecnologia (FCT) (PTDC/MED-OUT/1112/2021, UIDB/50026/2020, UIDP/50026/2020, NORTE-01-0145-FEDER-000039), EU’s Horizon 2020 (847507), “la Caixa” Foundation (ID 100010434) and FCT (LCF/PR/HR17/52190003), Gilead Research Scholars Program - Anti-Fungals, and EU-funded Horizon 2020 project HDM-FUN (ID 847507). M.R. and F.S. were supported by the DFG excellence graduate school Jena School for Microbial Communication, and C.C. by FCT (CEECIND/04058/2018).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCell Host Microbe. 2023 Mar 8;31(3):373-388.e10pt_PT
dc.identifier.doi10.1016/j.chom.2023.02.002pt_PT
dc.identifier.eissn1934-6069
dc.identifier.issn1931-3128
dc.identifier.urihttp://hdl.handle.net/10451/56653
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationNORTE-01-0145-FEDER-000039pt_PT
dc.relationLA - ICVS/3B's - Associate Laboratory
dc.relationLA - ICVS/3B's - Associate Laboratory
dc.relationHost directed medicine in invasive fungal infection
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/cell-host-and-microbept_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAspergillus fumigatuspt_PT
dc.subjectRab11pt_PT
dc.subjectRab7pt_PT
dc.subjectAnnexin A2pt_PT
dc.subjectExocytosispt_PT
dc.subjectHeat shock proteinpt_PT
dc.subjectHuman p11pt_PT
dc.subjectInvasive aspergillosispt_PT
dc.subjectPhagosome maturationpt_PT
dc.subjectRecycling endosomept_PT
dc.titleAspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathwaypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleLA - ICVS/3B's - Associate Laboratory
oaire.awardTitleLA - ICVS/3B's - Associate Laboratory
oaire.awardTitleHost directed medicine in invasive fungal infection
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMED-OUT%2F1112%2F2021/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50026%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50026%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/847507/EU
oaire.citation.endPage388.e10pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage373pt_PT
oaire.citation.titleCell Host & Microbept_PT
oaire.citation.volume31pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamH2020
person.familyNameLacerda
person.givenNameJoão
person.identifier559297
person.identifier.ciencia-id6412-2B63-2364
person.identifier.orcid0000-0003-1351-2809
person.identifier.scopus-author-id6603819609
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/10.13039/501100008530
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.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoveryafb302b1-8272-48de-b347-cb5b54a0a3da
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