Antifungal activity of flavonoids and modulation of expression of genes of fatty acid synthesis in the dermatophyte Trichophyton rubrum
Identifieur interne : 000159 ( Pmc/Checkpoint ); précédent : 000158; suivant : 000160Antifungal activity of flavonoids and modulation of expression of genes of fatty acid synthesis in the dermatophyte Trichophyton rubrum
Auteurs : Tamires Aparecida Bitencourt [Brésil] ; Tatiana Takahasikomoto [Brésil] ; Mozart Marins [Brésil] ; Ana Lúcia Fachin [Brésil]Source :
- BMC Proceedings ; 2014.
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DOI: 10.1186/1753-6561-8-S4-P53
PubMed: NONE
PubMed Central: 4204365
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Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author><author><name sortKey="Marins, Mozart" sort="Marins, Mozart" uniqKey="Marins M" first="Mozart" last="Marins">Mozart Marins</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author><author><name sortKey="Fachin, Ana Lucia" sort="Fachin, Ana Lucia" uniqKey="Fachin A" first="Ana Lúcia" last="Fachin">Ana Lúcia Fachin</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country 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Aparecida" uniqKey="Bitencourt T" first="Tamires Aparecida" last="Bitencourt">Tamires Aparecida Bitencourt</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author><author><name sortKey="Takahasikomoto, Tatiana" sort="Takahasikomoto, Tatiana" uniqKey="Takahasikomoto T" first="Tatiana" last="Takahasikomoto">Tatiana Takahasikomoto</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author><author><name sortKey="Marins, Mozart" sort="Marins, Mozart" uniqKey="Marins M" first="Mozart" last="Marins">Mozart Marins</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author><author><name sortKey="Fachin, Ana Lucia" sort="Fachin, Ana Lucia" uniqKey="Fachin A" first="Ana Lúcia" last="Fachin">Ana Lúcia Fachin</name><affiliation wicri:level="1"><nlm:aff id="I1">University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900</wicri:regionArea><wicri:noRegion>14096900</wicri:noRegion></affiliation></author></analytic><series><title level="j">BMC Proceedings</title><idno type="e-ISSN">1753-6561</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Martinez, Da" uniqKey="Martinez D">DA Martinez</name></author><author><name sortKey="Oliver, Bg" uniqKey="Oliver B">BG Oliver</name></author><author><name sortKey="Graser, Y" uniqKey="Graser Y">Y Graser</name></author><author><name sortKey="Goldberg, Jm" uniqKey="Goldberg J">JM Goldberg</name></author><author><name sortKey="Li, W" uniqKey="Li W">W Li</name></author><author><name sortKey="Martinez Rossi, Nm" uniqKey="Martinez Rossi N">NM Martinez-Rossi</name></author><author><name sortKey="Monod, M" uniqKey="Monod M">M Monod</name></author><author><name sortKey="Shelest, E" uniqKey="Shelest E">E Shelest</name></author><author><name sortKey="Barton, Rc" uniqKey="Barton R">RC Barton</name></author><author><name sortKey="Birch, E" uniqKey="Birch E">E Birch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Achterman, Rr" uniqKey="Achterman R">RR Achterman</name></author><author><name sortKey="White, Tc" uniqKey="White T">TC White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nir Paz, R" uniqKey="Nir Paz R">R Nir-Paz</name></author><author><name sortKey="Elinav, H" uniqKey="Elinav H">H Elinav</name></author><author><name sortKey="Pierard, Ge" uniqKey="Pierard G">GE Pierard</name></author><author><name sortKey="Walker, D" uniqKey="Walker D">D Walker</name></author><author><name sortKey="Maly, A" uniqKey="Maly A">A Maly</name></author><author><name sortKey="Shapiro, M" uniqKey="Shapiro M">M Shapiro</name></author><author><name sortKey="Barton, Rc" uniqKey="Barton R">RC Barton</name></author><author><name sortKey="Polacheck, I" uniqKey="Polacheck I">I Polacheck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Xc" uniqKey="Li X">XC Li</name></author><author><name sortKey="Joshi, As" uniqKey="Joshi A">AS Joshi</name></author><author><name sortKey="Elsohly, Hn" uniqKey="Elsohly H">HN ElSohly</name></author><author><name sortKey="Khan, Si" uniqKey="Khan S">SI Khan</name></author><author><name sortKey="Jacob, Mr" uniqKey="Jacob M">MR Jacob</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Khan, Ia" uniqKey="Khan I">IA Khan</name></author><author><name sortKey="Ferreira, D" uniqKey="Ferreira D">D Ferreira</name></author><author><name sortKey="Walker, La" uniqKey="Walker L">LA Walker</name></author><author><name sortKey="Broedel, Se" uniqKey="Broedel S">SE Broedel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rex, Jh" uniqKey="Rex J">JH Rex</name></author><author><name sortKey="Alexander, Bd" uniqKey="Alexander B">BD Alexander</name></author><author><name sortKey="Arthington Skaggs, B" uniqKey="Arthington Skaggs B">B Arthington-Skaggs</name></author><author><name sortKey="Brown, Sd" uniqKey="Brown S">SD Brown</name></author><author><name sortKey="Chaturveli, V" uniqKey="Chaturveli V">V Chaturveli</name></author><author><name sortKey="Espinel Ingroff, A" uniqKey="Espinel Ingroff A">A Espinel-Ingroff</name></author><author><name sortKey="Ghannoum, Ma" uniqKey="Ghannoum M">MA Ghannoum</name></author><author><name sortKey="Knapp, Cc" uniqKey="Knapp C">CC Knapp</name></author><author><name sortKey="Motyl, Mr" uniqKey="Motyl M">MR Motyl</name></author><author><name sortKey="Ostrosky Zeichner, L" uniqKey="Ostrosky Zeichner L">L Ostrosky-Zeichner</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="abstract" xml:lang="en"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Proc</journal-id><journal-id journal-id-type="iso-abbrev">BMC Proc</journal-id><journal-title-group><journal-title>BMC Proceedings</journal-title></journal-title-group><issn pub-type="epub">1753-6561</issn><publisher><publisher-name>BioMed Central</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">4204365</article-id><article-id pub-id-type="publisher-id">1753-6561-8-S4-P53</article-id><article-id pub-id-type="doi">10.1186/1753-6561-8-S4-P53</article-id><article-categories><subj-group subj-group-type="heading"><subject>Poster Presentation</subject></subj-group></article-categories><title-group><article-title>Antifungal activity of flavonoids and modulation of expression of genes of fatty acid synthesis in the dermatophyte <italic>Trichophyton rubrum</italic></article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Bitencourt</surname><given-names>Tamires Aparecida</given-names></name><xref ref-type="aff" rid="I1">1</xref></contrib><contrib contrib-type="author" id="A2"><name><surname>TakahasiKomoto</surname><given-names>Tatiana</given-names></name><xref ref-type="aff" rid="I1">1</xref></contrib><contrib contrib-type="author" id="A3"><name><surname>Marins</surname><given-names>Mozart</given-names></name><xref ref-type="aff" rid="I1">1</xref></contrib><contrib contrib-type="author" id="A4"><name><surname>Fachin</surname><given-names>Ana Lúcia</given-names></name><xref ref-type="aff" rid="I1">1</xref></contrib></contrib-group><aff id="I1"><label>1</label>University of Ribeirão Preto, Ribeirão Preto, São Paulo,14096900, Brazil</aff><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>1</day><month>10</month><year>2014</year></pub-date><volume>8</volume><issue>Suppl 4</issue><supplement><named-content content-type="supplement-title">The 5th Congress of the Brazilian Biotechnology Society (SBBIOTEC): Meeting abstracts</named-content><named-content content-type="supplement-editor">Luiz Antônio Barreto de Castro and Dario Grattapaglia</named-content><named-content content-type="supplement-sponsor">The publication charges for this supplement were funded by the Federal District Research Foundation Brazil - (Fundação de Amparo á Pesquisa do Distrito Federal (FAP-DF)-Brasil).</named-content></supplement><fpage>P53</fpage><lpage>P53</lpage><permissions><copyright-statement>Copyright © 2014 Bitencourt et al.; licensee BioMed Central Ltd.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Bitencourt et al.; licensee BioMed Central Ltd.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><self-uri xlink:href="http://www.biomedcentral.com/1753-6561/8/S4/P53"></self-uri><conference><conf-date>10-14 November 2013</conf-date><conf-name>5th Congress of the Brazilian Biotechnology Society (SBBIOTEC)</conf-name><conf-loc>Florianópolis, Brazil</conf-loc></conference></article-meta></front><body><sec><title>Background</title><p>Dermatophytosis are fungal infections caused by keratinophilic fungi known as dermatophytes and classified in three genera: <italic>Trichophyton, Epidermophyton and Microsporum. Trichophyton rubrum </italic>is the most frequent species associated to dermatophytosis worldwide [<xref ref-type="bibr" rid="B1">1</xref>]. The infections caused by dermatophytes are not lethal, but are difficult to treat and uncomfortable. In the case of <italic>T. rubrum</italic>, they tend to be chronic, and although the superficial infections are more common, cases of deep infection have been reported in immunocompromised patients [<xref ref-type="bibr" rid="B2">2</xref>][<xref ref-type="bibr" rid="B3">3</xref>]. The number of antifungal drugs are still limited, and the acquired resistance for some of clinical antifungal have been shown as well as the side effects that have been promoted by them. Reasons for the challenge in development of new antifungal drugs are the similarities shared by fungal and mammalian cells and the lack of knowledge about the biology of these pathogens. Recent evidences have shown that the fatty acid sinthase (FAS) is an interesting antifungal target [<xref ref-type="bibr" rid="B4">4</xref>] because of marked differences between human and fungal cells. The aim of this study was to evaluate the antifungal activity of four flavonoids described as FAS inhibitors and verify the modulation of genes in the pathway of fatty acid synthesis in <italic>T. rubrum </italic>growth in presence of the most effective one as FAS inhibitor.</p></sec><sec sec-type="methods"><title>Methods</title><p>The susceptibility assay was carried out using the microdilution test in RPMI medium in 96-well plates with the flavonoids quercetin, ellagic acid, galangin and genistein in a range of 1000-1.9µg/mL toward the strain ATCC MYA-3108 of <italic>T. rubrum </italic>[<xref ref-type="bibr" rid="B5">5</xref>]. The modulation of genes fatty acid synthesis(FAS 1p, FAS 2p subunits), acetyl-COA carboxylase 2p subunity and fatty acid transporter protein (<italic>FAT</italic>1) was analyzed by quantitative PCR using Sybr Green after 16h of incubation of strain of <italic>T.rubrum </italic>with MIC of quercetin in liquid Sabouraud medium.</p></sec><sec><title>Results and conclusion</title><p>Quercetin showed the most effective antifungal activity with MIC of 125 µg/mL, ellagic acid presented MIC of 250 µg/mL, galangin and genistein were ineffective toward <italic>T.rubrum (</italic>MIC >1000 µg/mL). The positive controls fluconazole and cerulenin presented MICs of 63 and 125 µg/mL, respectively. The analyse of gene expression of the fatty acid synthetic pathway showed the majority of the genes were downregulated by quercetin, fluconazole and cerulenin. However, cerulenin caused a low upregulation of <italic>FAS</italic>2p gene. Thus, the results suggest the activity of quercetin could be due the modulation of genes of the pathway of fatty acid synthesis, which is a fungal specific target for development of antifungal drugs.</p></sec></body><back><sec><title>Acknowledgements</title><p>This study was supported by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (2012/02920-7 and 2009/12419-0) and CAPES.</p></sec><ref-list><ref id="B1"><mixed-citation 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