Trans-chalcone and quercetin down-regulate fatty acid synthase gene expression and reduce ergosterol content in the human pathogenic dermatophyte Trichophyton rubrum
Identifieur interne : 000212 ( Main/Exploration ); précédent : 000211; suivant : 000213Trans-chalcone and quercetin down-regulate fatty acid synthase gene expression and reduce ergosterol content in the human pathogenic dermatophyte Trichophyton rubrum
Auteurs : Tamires Aparecida Bitencourt [Brésil] ; Tatiana Takahasi Komoto [Brésil] ; Bruna Gabriele Massaroto [Brésil] ; Carlos Eduardo Saraiva Miranda [Brésil] ; Rene Oliveira Beleboni [Brésil] ; Mozart Marins [Brésil] ; Ana Lúcia Fachin [Brésil]Source :
- BMC Complementary and Alternative Medicine ; 2013.
Abstract
Fatty acid synthase (FAS) is a promising antifungal target due to its marked structural differences between fungal and mammalian cells. The aim of this study was to evaluate the antifungal activity of flavonoids described in the scientific literature as FAS inhibitors (quercetin, trans-chalcone, ellagic acid, luteolin, galangin, and genistein) against the dermatophyte
The antifungal activity of the natural products was tested by the microdilution assay for determination of the minimum inhibitory concentration (MIC). The effect of the compounds on the cell membrane was evaluated using a protoplast regeneration assay. Ergosterol content was quantified by spectrophotometry. Inhibition of FAS by flavonoids was evaluated by an enzymatic assay to determine IC50 values. Quantitative RT-PCR was used to measure transcription levels of the
The flavonoids quercetin and trans-chalcone were effective against
Trans-chalcone and quercetin showed antifungal activity against
Url:
DOI: 10.1186/1472-6882-13-229
PubMed: 24044691
PubMed Central: 3849095
Affiliations:
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uniqKey="Komoto T" first="Tatiana Takahasi" last="Komoto">Tatiana Takahasi Komoto</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Massaroto, Bruna Gabriele" sort="Massaroto, Bruna Gabriele" uniqKey="Massaroto B" first="Bruna Gabriele" last="Massaroto">Bruna Gabriele Massaroto</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade 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Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Komoto, Tatiana Takahasi" sort="Komoto, Tatiana Takahasi" uniqKey="Komoto T" first="Tatiana Takahasi" last="Komoto">Tatiana Takahasi Komoto</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Massaroto, Bruna Gabriele" sort="Massaroto, Bruna Gabriele" uniqKey="Massaroto B" first="Bruna Gabriele" last="Massaroto">Bruna Gabriele Massaroto</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Miranda, Carlos Eduardo Saraiva" sort="Miranda, Carlos Eduardo Saraiva" uniqKey="Miranda C" first="Carlos Eduardo Saraiva" last="Miranda">Carlos Eduardo Saraiva Miranda</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Beleboni, Rene Oliveira" sort="Beleboni, Rene Oliveira" uniqKey="Beleboni R" first="Rene Oliveira" last="Beleboni">Rene Oliveira Beleboni</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Marins, Mozart" sort="Marins, Mozart" uniqKey="Marins M" first="Mozart" last="Marins">Mozart Marins</name><affiliation wicri:level="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></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="2"><nlm:aff id="I1">Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP, Brasil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Unidade de Biotecnologia, Universidade de Ribeirão Preto, Av: Costábile Romano 2201, 14096-900, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author></analytic><series><title level="j">BMC Complementary and Alternative Medicine</title><idno type="e-ISSN">1472-6882</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Fatty acid synthase (FAS) is a promising antifungal target due to its marked structural differences between fungal and mammalian cells. The aim of this study was to evaluate the antifungal activity of flavonoids described in the scientific literature as FAS inhibitors (quercetin, trans-chalcone, ellagic acid, luteolin, galangin, and genistein) against the dermatophyte <italic>Trichophyton rubrum</italic> and their effects on fatty acid and ergosterol synthesis.</p></sec><sec><title>Methods</title><p>The antifungal activity of the natural products was tested by the microdilution assay for determination of the minimum inhibitory concentration (MIC). The effect of the compounds on the cell membrane was evaluated using a protoplast regeneration assay. Ergosterol content was quantified by spectrophotometry. Inhibition of FAS by flavonoids was evaluated by an enzymatic assay to determine IC<sub>50</sub> values. Quantitative RT-PCR was used to measure transcription levels of the <italic>FAS1</italic> and <italic>ERG6</italic> genes involved in fatty acid and ergosterol biosynthesis, respectively, during exposure of <italic>T. rubrum</italic> to the flavonoids tested.</p></sec><sec><title>Results</title><p>The flavonoids quercetin and trans-chalcone were effective against <italic>T. rubrum</italic>, with MICs of 125 and 7.5 μg/mL for the wild-type strain (MYA3108) and of 63 and 1.9 μg/mL for the ABC transporter mutant strain (Δ<italic>TruMDR2)</italic>, respectively. The MICs of the fluconazole and cerulenin controls were 63 and 125 μg/mL for the wild-type strain and 30 and 15 μg/mL for the mutant strain, respectively. Quercetin and trans-chalcone also reduced ergosterol content in the two strains, indicating that interference with fatty acid and ergosterol synthesis caused cell membrane disruption. The MIC of quercetin reduced the number of regenerated protoplasts by 30.26% (wild-type strain) and by 91.66% (mutant strain). Half the MIC (0.5 MIC) of quercetin did not reduce the number of regenerated wild-type fungal colonies, but caused a 36.19% reduction in the number of mutant strain protoplasts. In contrast, the MIC and 0.5 MIC of trans-chalcone and cerulenin drastically reduced protoplast regeneration in the two strains. The <italic>FAS1</italic> gene was repressed in the presence of MICs of quercetin, trans-chalcone, fluconazole and cerulenin. The <italic>ERG6</italic> gene was induced in the presence of MICs of fluconazole and cerulenin and was repressed in the presence of MICs of trans-chalcone and quercetin. Trans-chalcone and quercetin inhibited the enzymatic activity of FAS, with IC<sub>50</sub> values of 68.23 and 17.1 μg/mL, respectively.</p></sec><sec><title>Conclusion</title><p>Trans-chalcone and quercetin showed antifungal activity against <italic>T. rubrum</italic>, reducing ergosterol levels and modulating the expression of <italic>FAS1</italic> and <italic>ERG6</italic>.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Marconi, Vc" uniqKey="Marconi V">VC Marconi</name></author><author><name sortKey="Kradin, R" uniqKey="Kradin R">R Kradin</name></author><author><name sortKey="Marty, Fm" uniqKey="Marty F">FM Marty</name></author><author><name sortKey="Hospenthal, Dr" uniqKey="Hospenthal D">DR Hospenthal</name></author><author><name sortKey="Kotton, Cn" uniqKey="Kotton C">CN Kotton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ameen, M" uniqKey="Ameen M">M 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sortKey="Kim, Hn" uniqKey="Kim H">HN Kim</name></author><author><name sortKey="Kim, Hk" uniqKey="Kim H">HK Kim</name></author><author><name sortKey="Kim, Pi" uniqKey="Kim P">PI Kim</name></author><author><name sortKey="Choi, Bh" uniqKey="Choi B">BH Choi</name></author><author><name sortKey="Hahm, K S" uniqKey="Hahm K">K-S Hahm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Young, Ly" uniqKey="Young L">LY Young</name></author><author><name sortKey="Hull, Cm" uniqKey="Hull C">CM Hull</name></author><author><name sortKey="Heitman, J" uniqKey="Heitman J">J Heitman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name></author><author><name sortKey="Yu, L" uniqKey="Yu L">L Yu</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Peng, J" uniqKey="Peng J">J Peng</name></author><author><name sortKey="Jin, Q" uniqKey="Jin Q">Q Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barker, Ks" uniqKey="Barker K">KS Barker</name></author><author><name sortKey="Crisp, S" uniqKey="Crisp S">S Crisp</name></author><author><name sortKey="Wiederhold, N" uniqKey="Wiederhold N">N Wiederhold</name></author><author><name sortKey="Lewis, Re" uniqKey="Lewis R">RE Lewis</name></author><author><name sortKey="Bareither, B" uniqKey="Bareither B">B Bareither</name></author><author><name sortKey="Eckstein, J" uniqKey="Eckstein J">J Eckstein</name></author><author><name sortKey="Barbuch, R" uniqKey="Barbuch R">R Barbuch</name></author><author><name sortKey="Bard, M" uniqKey="Bard M">M Bard</name></author><author><name sortKey="Rogers, Pd" uniqKey="Rogers P">PD Rogers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leber, R" uniqKey="Leber R">R Leber</name></author><author><name sortKey="Zinser, E" uniqKey="Zinser E">E Zinser</name></author><author><name sortKey="Hrastnik, C" uniqKey="Hrastnik C">C Hrastnik</name></author><author><name sortKey="Paltauf, F" uniqKey="Paltauf F">F Paltauf</name></author><author><name sortKey="Daum, G" uniqKey="Daum G">G Daum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pinto, Wj" uniqKey="Pinto W">WJ Pinto</name></author><author><name sortKey="Lozano, R" uniqKey="Lozano R">R Lozano</name></author><author><name sortKey="Nes, Wr" uniqKey="Nes W">WR Nes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Servouse, M" uniqKey="Servouse M">M Servouse</name></author><author><name sortKey="Karst, F" uniqKey="Karst F">F Karst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Casey, Wm" uniqKey="Casey W">WM Casey</name></author><author><name sortKey="Keesler, Ga" uniqKey="Keesler G">GA Keesler</name></author><author><name sortKey="Parks, Lw" uniqKey="Parks L">LW Parks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Sj" uniqKey="Smith S">SJ Smith</name></author><author><name sortKey="Crowley, Jh" uniqKey="Crowley J">JH Crowley</name></author><author><name sortKey="Parks, Lw" uniqKey="Parks L">LW Parks</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Brésil</li></country><region><li>État de São Paulo</li></region></list><tree><country name="Brésil"><region name="État de São Paulo"><name sortKey="Bitencourt, Tamires Aparecida" sort="Bitencourt, Tamires Aparecida" uniqKey="Bitencourt T" first="Tamires Aparecida" last="Bitencourt">Tamires Aparecida Bitencourt</name></region><name sortKey="Beleboni, Rene Oliveira" sort="Beleboni, Rene Oliveira" uniqKey="Beleboni R" first="Rene Oliveira" last="Beleboni">Rene Oliveira Beleboni</name><name sortKey="Fachin, Ana Lucia" sort="Fachin, Ana Lucia" uniqKey="Fachin A" first="Ana Lúcia" last="Fachin">Ana Lúcia Fachin</name><name sortKey="Komoto, Tatiana Takahasi" sort="Komoto, Tatiana Takahasi" uniqKey="Komoto T" first="Tatiana Takahasi" last="Komoto">Tatiana Takahasi Komoto</name><name sortKey="Marins, Mozart" sort="Marins, Mozart" uniqKey="Marins M" first="Mozart" last="Marins">Mozart Marins</name><name sortKey="Massaroto, Bruna Gabriele" sort="Massaroto, Bruna Gabriele" uniqKey="Massaroto B" first="Bruna Gabriele" last="Massaroto">Bruna Gabriele Massaroto</name><name sortKey="Miranda, Carlos Eduardo Saraiva" sort="Miranda, Carlos Eduardo Saraiva" uniqKey="Miranda C" first="Carlos Eduardo Saraiva" last="Miranda">Carlos Eduardo Saraiva Miranda</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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