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dc.contributor.authorOyola, Samuel O.
dc.contributor.authorEvans, Krystal J.
dc.contributor.authorSmith, Terry K.
dc.contributor.authorSmith, Barbara A.
dc.contributor.authorHilley, James D.
dc.contributor.authorMottram, Jeremy C.
dc.contributor.authorKaye, Paul M.
dc.contributor.authorSmith, Deborah F.
dc.date.accessioned2013-02-11T16:31:06Z
dc.date.available2013-02-11T16:31:06Z
dc.date.issued2012-12-10
dc.identifier.citationOyola , S O , Evans , K J , Smith , T K , Smith , B A , Hilley , J D , Mottram , J C , Kaye , P M & Smith , D F 2012 , ' Functional analysis of Leishmania cyclopropane fatty acid synthetase ' PLoS One , vol. 7 , no. 12 , e51300 . https://doi.org/10.1371/journal.pone.0051300en
dc.identifier.issn1932-6203
dc.identifier.otherPURE: 45307791
dc.identifier.otherPURE UUID: 65212994-0eb2-415a-9d43-ea58ff92dce0
dc.identifier.otherWOS: 000312201900063
dc.identifier.otherPubMed: 23251490
dc.identifier.otherScopus: 84870922577
dc.identifier.urihttp://hdl.handle.net/10023/3354
dc.description.abstractThe single gene encoding cyclopropane fatty acid synthetase (CFAS) is present in Leishmania infantum, L. mexicana and L. braziliensis but absent from L. major, a causative agent of cutaneous leishmaniasis. In L. infantum, usually causative agent of visceral leishmaniasis, the CFAS gene is transcribed in both insect (extracellular) and host (intracellular) stages of the parasite life cycle. Tagged CFAS protein is stably detected in intracellular L. infantum but only during the early log phase of extracellular growth, when it shows partial localisation to the endoplasmic reticulum. Lipid analyses of L. infantum wild type, CFAS null and complemented parasites detect a low abundance CFAS-dependent C19 Delta fatty acid, characteristic of a cyclopropanated species, in wild type and add-back cells. Sub-cellular fractionation studies locate the C19 Delta fatty acid to both ER and plasma membrane-enriched fractions. This fatty acid is not detectable in wild type L. major, although expression of the L. infantum CFAS gene in L. major generates cyclopropanated fatty acids, indicating that the substrate for this modification is present in L. major, despite the absence of the modifying enzyme. Loss of the L. infantum CFAS gene does not affect extracellular parasite growth, phagocytosis or early survival in macrophages. However, while endocytosis is also unaffected in the extracellular CFAS nulls, membrane transporter activity is defective and the null parasites are more resistant to oxidative stress. Following infection in vivo, L. infantum CFAS nulls exhibit lower parasite burdens in both the liver and spleen of susceptible hosts but it has not been possible to complement this phenotype, suggesting that loss of C19 Delta fatty acid may lead to irreversible changes in cell physiology that cannot be rescued by re-expression. Aberrant cyclopropanation in L. major decreases parasite virulence but does not influence parasite tissue tropism.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofPLoS Oneen
dc.rights© 2012 Oyola et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectEscherichia-colien
dc.subjectSynthaseen
dc.subjectGene-expressionen
dc.subjectDrug-resistanceen
dc.subjectMycobacterium-tuberculosisen
dc.subjectMolecular-cloningen
dc.subjectDonovanien
dc.subjectInfective stagesen
dc.subjectMycolic acidsen
dc.subjectTrypanosoma-bruceien
dc.subjectQP Physiologyen
dc.subjectQD Chemistryen
dc.subjectQR Microbiologyen
dc.subject.lccQPen
dc.subject.lccQDen
dc.subject.lccQRen
dc.titleFunctional analysis of Leishmania cyclopropane fatty acid synthetaseen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0051300
dc.description.statusPeer revieweden


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