Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Metabolic modeling of antibiotic and cytotoxic effects of the isoquinoline IQ-238 in S. aureus, S. epidermidis and human cells

ABSTRACT: Isoquinolines (IQs) are natural substances with antibiotic potential. IQ-238 is a synthetic analog of the novel-type N,C-coupled naphtylisoquinoline (NIQ) alkaloid ancisheynine. Gene expression data, cytotoxicity measurements and metabolic modelling is combined to assess the effects of the N,C-coupled naphtylisoquinoline (NIQ) compound IQ-238 on Staphylococcus aureus and man as a potential lead for novel antibiotics. It possesses a high activity against staphylococci but has low cytotoxicity in human cell lines. Genome annotation identified missed enzymes (validated by PCR) in the primary (e.g. nucleotide) metabolism of staphylococci. Gene expression changed after cultivation with IQ-238. Metabolic modelling did yield the adaptations of all central enzymes, including those not affected by significant gene expression changes. The data show that IQ-238 interferes with the carbohydrate metabolism in staphylococci. The data suggest that IQ-238 is a promising lead for antibiotic therapy against S. aureus infections. HG001 WT strain exposed to GB-AP-238 in rich medium

ORGANISM(S): Staphylococcus aureus

SUBMITTER: FRANCOIS Patrice

PROVIDER: E-GEOD-33832 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Modelling antibiotic and cytotoxic isoquinoline effects in Staphylococcus aureus, Staphylococcus epidermidis and mammalian cells.

Cecil Alexander A Ohlsen Knut K Menzel Thomas T François Patrice P Schrenzel Jacques J Fischer Adrien A Dörries Kirsten K Selle Martina M Lalk Michael M Hantzschmann Julia J Dittrich Marcus M Liang Chunguang C Bernhardt Jörg J Ölschläger Tobias A TA Bringmann Gerhard G Bruhn Heike H Unger Matthias M Ponte-Sucre Alicia A Lehmann Leane L Dandekar Thomas T

International journal of medical microbiology : IJMM 20141127 1

Isoquinolines (IQs) are natural substances with an antibiotic potential we aim to optimize. Specifically, IQ-238 is a synthetic analog of the novel-type N,C-coupled naphthylisoquinoline (NIQ) alkaloid ancisheynine. Recently, we developed and tested other IQs such as IQ-143. By utilizing genome-wide gene expression data, metabolic network modelling and Voronoi tessalation based data analysis - as well as cytotoxicity measurements, chemical properties calculations and principal component analysis ...[more]

PMID: 25500547

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Dataset Information

Metabolic modeling of antibiotic and cytotoxic effects of the isoquinoline IQ-238 in S. aureus, S. epidermidis and human cells

Publications

Modelling antibiotic and cytotoxic isoquinoline effects in Staphylococcus aureus, Staphylococcus epidermidis and mammalian cells.

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