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dc.contributor.authorHeinz, E.
dc.contributor.authorHacker, C.
dc.contributor.authorDean, P.
dc.contributor.authorMifsud, J.
dc.contributor.authorGoldberg, A.V.
dc.contributor.authorWilliams, T.A.
dc.contributor.authorNakjang, S.
dc.contributor.authorGregory, A.
dc.contributor.authorHirt, R.P.
dc.contributor.authorLucocq, John M.
dc.contributor.authorKunji, E.R.S.
dc.contributor.authorEmbley, T.M.
dc.date.accessioned2015-02-02T12:01:05Z
dc.date.available2015-02-02T12:01:05Z
dc.date.issued2014-12-04
dc.identifier.citationHeinz , E , Hacker , C , Dean , P , Mifsud , J , Goldberg , A V , Williams , T A , Nakjang , S , Gregory , A , Hirt , R P , Lucocq , J M , Kunji , E R S & Embley , T M 2014 , ' Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites ' , PLoS Pathogens , vol. 10 , no. 12 , e1004547 . https://doi.org/10.1371/journal.ppat.1004547en
dc.identifier.issn1553-7366
dc.identifier.otherPURE: 164467247
dc.identifier.otherPURE UUID: 12e62d0b-2216-4259-b48f-7725e2ebb675
dc.identifier.otherScopus: 84919625032
dc.identifier.otherWOS: 000346702400032
dc.identifier.otherORCID: /0000-0002-5191-0093/work/64361204
dc.identifier.urihttp://hdl.handle.net/10023/6048
dc.descriptionEH and TAW acknowledge support from the Marie Curie Fellowship Programme (HTTP://cordis.europa.eu/fp7/home_en.html). ERSK, JML and TME acknowledge support from the Wellcome Trust (www.wellcome.ac.uk/). ERSK acknowledges support from the Medical Research Council (www.mrc.ac.uk). TME acknowledges support from the European Research Council Advanced Investigator Programme (http://erc.europa.eu/advanced-grants).en
dc.description.abstractMicrosporidia are obligate intracellular parasites of most animal groups including humans, but despite their significant economic and medical importance there are major gaps in our understanding of how they exploit infected host cells. We have investigated the evolution, cellular locations and substrate specificities of a family of nucleotide transport (NTT) proteins from Trachipleistophora hominis, a microsporidian isolated from an HIV/AIDS patient. Transport proteins are critical to microsporidian success because they compensate for the dramatic loss of metabolic pathways that is a hallmark of the group. Our data demonstrate that the use of plasma membrane-located nucleotide transport proteins (NTT) is a key strategy adopted by microsporidians to exploit host cells. Acquisition of an ancestral transporter gene at the base of the microsporidian radiation was followed by lineage-specific events of gene duplication, which in the case of T. hominis has generated four paralogous NTT transporters. All four T. hominis NTT proteins are located predominantly to the plasma membrane of replicating intracellular cells where they can mediate transport at the host-parasite interface. In contrast to published data for Encephalitozoon cuniculi, we found no evidence for the location for any of the T. hominis NTT transporters to its minimal mitochondria (mitosomes), consistent with lineage-specific differences in transporter and mitosome evolution. All of the T. hominis NTTs transported radiolabelled purine nucleotides (ATP, ADP, GTP and GDP) when expressed in Escherichia coli, but did not transport radiolabelled pyrimidine nucleotides. Genome analysis suggests that imported purine nucleotides could be used by T. hominis to make all of the critical purine-based building-blocks for DNA and RNA biosynthesis during parasite intracellular replication, as well as providing essential energy for parasite cellular metabolism and protein synthesis.
dc.language.isoeng
dc.relation.ispartofPLoS Pathogensen
dc.rightsCopyright © 2014 Embley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectR Medicine (General)en
dc.subjectBDCen
dc.subject.lccR1en
dc.titlePlasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasitesen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1004547
dc.description.statusPeer revieweden
dc.identifier.urlhttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004547#s4en


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