Selectivity of TMC207 towards Mycobacterial ATP Synthase Compared with That towards the Eukaryotic Homologue

被引：181

作者：

Haagsma, Anna C. ^{[1
]}

Abdillahi-Ibrahim, Rooda ^{[1
]}

Wagner, Marijke J. ^{[1
]}

Krab, Klaas ^{[1
]}

Vergauwen, Karen ^{[2
]}

Guillemont, Jerome ^{[2
]}

Andries, Koen ^{[2
]}

Lill, Holger ^{[1
]}

Koul, Anil ^{[2
]}

Bald, Dirk ^{[1
]}

机构：

[1] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Mol Cell Biol, NL-1081 HV Amsterdam, Netherlands

[2] Johnson & Johnson Pharmaceut Res & Dev, Dept Antimicrobial Res, B-2340 Beerse, Belgium

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2009年 / 53卷 / 03期

关键词：

RAT-LIVER MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; SUBMITOCHONDRIAL PARTICLES; TUBERCULOSIS; DIARYLQUINOLINES; HOMEOSTASIS; MECHANISM; TOXICITY; R207910; ENZYME;

D O I：

10.1128/AAC.01393-08

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

The diarylquinoline TMC207 kills Mycobacterium tuberculosis by specifically inhibiting ATP synthase. We show here that human mitochondrial ATP synthase (50% inhibitory concentration [IC50] of >200 mu M) displayed more than 20,000-fold lower sensitivity for TMC207 compared to that of mycobacterial ATP synthase (IC50 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.

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收藏

页码：1290 / 1292

页数：3

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