Editor: Dieter Jahn
ATP synthase in slow- and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction
Version of Record online: 7 OCT 2010
© 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
FEMS Microbiology Letters
Volume 313, Issue 1, pages 68–74, December 2010
How to Cite
Haagsma, A. C., Driessen, N. N., Hahn, M.-M., Lill, H. and Bald, D. (2010), ATP synthase in slow- and fast-growing mycobacteria is active in ATP synthesis and blocked in ATP hydrolysis direction. FEMS Microbiology Letters, 313: 68–74. doi: 10.1111/j.1574-6968.2010.02123.x
- Issue online: 9 NOV 2010
- Version of Record online: 7 OCT 2010
- Accepted manuscript online: 24 SEP 2010 12:00AM EST
- Received 6 July 2010; revised 14 September 2010; accepted 15 September 2010.Final version published online 7 October 2010.
- ATP synthase;
- antimycobacterial drugs;
ATP synthase is a validated drug target for the treatment of tuberculosis, and ATP synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as Mycobacterium leprae and Mycobacterium ulcerans. ATP synthase is an essential enzyme in the energy metabolism of Mycobacterium tuberculosis; however, no biochemical data are available to characterize the role of ATP synthase in slow-growing mycobacterial strains. Here, we show that inverted membrane vesicles from the slow-growing model strain Mycobacterium bovis BCG are active in ATP synthesis, but ATP synthase displays no detectable ATP hydrolysis activity and does not set up a proton-motive force (PMF) using ATP as a substrate. Treatment with methanol as well as PMF activation unmasked the ATP hydrolysis activity, indicating that the intrinsic subunit ɛ and inhibitory ADP are responsible for the suppression of hydrolytic activity. These results suggest that the enzyme is needed for the synthesis of ATP, not for the maintenance of the PMF. For the development of new antimycobacterial drugs acting on ATP synthase, screening for ATP synthesis inhibitors, but not for ATP hydrolysis blockers, can be regarded as a promising strategy.