Selectivity of TMC207 towards Mycobacterial ATP Synthase Compared with That towards the Eukaryotic Homologue
-
- Anna C. Haagsma
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
-
- Rooda Abdillahi-Ibrahim
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
-
- Marijke J. Wagner
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
-
- Klaas Krab
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
-
- Karen Vergauwen
- Department of Antimicrobial Research, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
-
- Jerome Guillemont
- Department of Antimicrobial Research, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
-
- Koen Andries
- Department of Antimicrobial Research, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
-
- Holger Lill
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
-
- Anil Koul
- Department of Antimicrobial Research, Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
-
- Dirk Bald
- Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
書誌事項
- 公開日
- 2009-03
- 権利情報
-
- https://journals.asm.org/non-commercial-tdm-license
- DOI
-
- 10.1128/aac.01393-08
- 公開者
- American Society for Microbiology
この論文をさがす
説明
<jats:title>ABSTRACT</jats:title> <jats:p> The diarylquinoline TMC207 kills <jats:italic>Mycobacterium tuberculosis</jats:italic> by specifically inhibiting ATP synthase. We show here that human mitochondrial ATP synthase (50% inhibitory concentration [IC <jats:sub>50</jats:sub> ] of >200 μM) displayed more than 20,000-fold lower sensitivity for TMC207 compared to that of mycobacterial ATP synthase (IC <jats:sub>50</jats:sub> of 10 nM). Also, oxygen consumption in mouse liver and bovine heart mitochondria showed very low sensitivity for TMC207. These results suggest that TMC207 may not elicit ATP synthesis-related toxicity in mammalian cells. ATP synthase, although highly conserved between prokaryotes and eukaryotes, may still qualify as an attractive antibiotic target. </jats:p>
収録刊行物
-
- Antimicrobial Agents and Chemotherapy
-
Antimicrobial Agents and Chemotherapy 53 (3), 1290-1292, 2009-03
American Society for Microbiology