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Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni

2005Journal article Restricted
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dc.contributor.authorElandalloussi, Laurence M.
dc.contributor.authorRodrigues, Pedro
dc.contributor.authorAfonso, Ricardo
dc.contributor.authorLeite, Ricardo
dc.contributor.authorNunes, Patrícia A.
dc.contributor.authorCancela, Leonor
dc.date.accessioned2014-06-18T09:46:09Z
dc.date.available2014-06-18T09:46:09Z
dc.date.issued2005
dc.date.updated2014-06-12T13:35:46Z
dc.description.abstractWe have exploited the experimental accessibility of the protozoan parasite Perkinsus olseni and its similarities to apicomplexan parasites to investigate the influence of specific drugs on its proliferation. For this purpose, shikimate and folate pathways present an attractive target for parasitic therapy given their major differences with mammalian pathways. Glyphosate, a potent inhibitor of the shikimate pathway enzyme EPSP synthase inhibited the in vitro proliferation of P. olseni in a dose-dependent manner and this effectwas reversed by addition of chorismate, indicating the presence of a shikimate pathway. However, this effect was not antagonised by p-aminobenzoate or folic acid. Furthermore, antagonism was observed, via pyrimethamine to glyphosate inhibitory effect, suggesting that the shikimate pathway is not essential for the biosynthesis of folate precursors and is therefore crucial for another pathway downstream from chorismate. In addition, sulfadiazine, a well known inhibitor of dihydropteorate synthase, an enzyme of the folate biosynthetic pathway,had no inhibitory effect on P. olseni proliferation. In view of these results, the parasite does not appear to require the folate biosynthesis pathway for its survival and is most likely able to use exogenous folate. Even though pyrimethamine was found to inhibit P. atlanticus growth, this inhibitory effect could not be reversed by co-addition of folic acid. Therefore, we propose that the effect of pyrimethamine observed in this study results from the inhibition of a target other than dihydrofolate reductase. Similarly, proguanil target is likely to be separate from DHFR since only its metabolite cycloguanil has been shown to have inhibitory properties on DHFR.por
dc.identifier.citationElandalloussi, Laurence M.; Rodrigues, Pedro M.; Afonso, Ricardo; Leite, Ricardo B.; Nunes, Patrícia A.; Cancela, M. Leonor. Shikimate and folate pathways in the protozoan parasite, Perkinsus olseni, Molecular and Biochemical Parasitology, 142, 1, 106-109, 2005.por
dc.identifier.doihttp://dx.doi.org/10.1016/j.molbiopara.2005.03.014
dc.identifier.issn0166-6851
dc.identifier.otherAUT: PMR01268; LCA00739;
dc.identifier.urihttp://hdl.handle.net/10400.1/4362
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherElsevierpor
dc.subjectPerkinsus olsenipor
dc.subjectPerkinsus atlanticuspor
dc.subjectProtozoan parasitepor
dc.subjectShikimate pathwaypor
dc.subjectFolatepor
dc.titleShikimate and folate pathways in the protozoan parasite, Perkinsus olsenipor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage109por
oaire.citation.issue1por
oaire.citation.startPage106por
oaire.citation.titleMolecular and Biochemical Parasitologypor
oaire.citation.volume142por
person.familyNameRodrigues
person.familyNameAfonso
person.familyNameLeite
person.familyNameNunes Cabrita
person.familyNameCancela
person.givenNamePedro
person.givenNameRicardo
person.givenNameRicardo
person.givenNamePatrícia
person.givenNameM. Leonor
person.identifier447622
person.identifier.ciencia-idF115-256E-C84D
person.identifier.orcid0000-0002-9668-1204
person.identifier.orcid0000-0002-3884-9312
person.identifier.orcid0000-0002-9622-3895
person.identifier.orcid0000-0002-7148-8950
person.identifier.orcid0000-0003-3114-6662
person.identifier.ridM-3406-2013
person.identifier.ridB-3389-2008
person.identifier.scopus-author-id55107531000
person.identifier.scopus-author-id8362650900
person.identifier.scopus-author-id7006823084
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationc4613fe6-e1a0-4dd9-be8d-442b2b8a7b72
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relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication.latestForDiscovery30644154-3327-45af-a3ed-f5e221951b4c

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