Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus,. | Cecil et al. Genome Biology 2011 12 R24 http 2011 12 3 R24 Genome Biology RESEARCH Open Access Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus Staphylococcus epidermidis and human cells A I Ịz l x z f r- I I 1 h í D I lz zz z 1I z 2 h I i rs I I r 3 h t m 1I I 1 I zz D I zz l -4 I z I .z A AA z-z I r- r- 1 I .z Z- 3 Alexander Cecil carina RiKanovic Knut Ohlsen Chunguang Liang Jorg Bernhardt lobias A ueiscniaeger I AAI I I 4 x z5 6 r 4 D z IZ- z zz 5 I I zì lzzz I I I ZZ. iI I z 1 2 n A I r I Ì z zz 4 Z Izz z 1 7 lanja Guider Gerhard Bringmann Uirike noizgraoe Matthias Unger and Thomas DandeKar Abstract Background Xenobiotics represent an environmentai stress and as such are a source for antibiotics inciuding the isoquinoiine IQ compound IQ-143. Here we demonstrate the utiiity of compiementary anaiysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143 a synthetic anaiog of the novei type N C-coupied naphthyi-isoquinoiine aiKaioid ancisheynine. Results Metaboiite measurements gene expression data and functionai assays were combined with metaboiic modeiing to assess the effects of IQ-143 on Staphylococcus aureus Staphylococcus epidermidis and human ceii iines as a potentiai paradigm for novei antibiotics. Genome annotation and PCR vaiidation identified novei enzymes in the primary metaboiism of staphyiococci. Gene expression response analysis and metaboiic modeiing demonstrated the adaptation of enzymes to IQ-143 including those not affected by significant gene expression changes. At iower concentrations IQ-143 was bacteriostatic and at higher concentrations bactericidai whiie the anaiysis suggested that the mode of action was a direct interference in nucieotide and energy metaboiism. Experiments in human ceii iines supported the conciusions from pathway modeiing and found that IQ-143 had iow cytotoxicity. Conclusions The data suggest .
