The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 40 of 74
Back to Result List

Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-68802
  • Background: Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Results: Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on StaphylococcusBackground: Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Results: Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on Staphylococcus aureus, Staphylococcus epidermidis and human cell lines, as a potential paradigm for novel antibiotics. Genome annotation and PCR validation identified novel enzymes in the primary metabolism of staphylococci. Gene expression response analysis and metabolic modeling demonstrated the adaptation of enzymes to IQ-143, including those not affected by significant gene expression changes. At lower concentrations, IQ-143 was bacteriostatic, and at higher concentrations bactericidal, while the analysis suggested that the mode of action was a direct interference in nucleotide and energy metabolism. Experiments in human cell lines supported the conclusions from pathway modeling and found that IQ-143 had low cytotoxicity. Conclusions: The data suggest that IQ-143 is a promising lead compound for antibiotic therapy against staphylococci. The combination of gene expression and metabolite analyses with in silico modeling of metabolite pathways allowed us to study metabolic adaptations in detail and can be used for the evaluation of metabolic effects of other xenobiotics.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Alexander Cecil, Carina Rikanovic, Knut Ohlsen, Chunguang Liang, Jorg Bernhardt, Tobias A. Oelschlaeger, Tanja Gulder, Gerd Bringmann, Ulrike Holzgrabe, Matthias Unger, Thomas Dandekar
URN:urn:nbn:de:bvb:20-opus-68802
Document Type:Journal article
Faculties:Fakultät für Chemie und Pharmazie / Institut für Organische Chemie
Language:English
Year of Completion:2011
Source:In: Genome Biology (2011) 12:R24, doi: 10.1186/gb-2011-12-3-r24
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
GND Keyword:Staphylococcus aureus
Release Date:2012/11/15
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2011
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung