Bedaquiline (BDQ), an inhibitor of the mycobacterial F1Fo-ATP synthase, has revolutionized the antitubercular drug discovery program by defining energy metabolism as a potent new target space. Several studies have recently suggested that BDQ ultimately causes mycobacterial cell death through a phenomenon known as uncoupling. The biochemical basis underlying this, in BDQ, is unresolved and may represent a new pathway to the development of effective therapeutics. In this communication, we demonstrate that BDQ can inhibit ATP synthesis in Escherichia coli by functioning as a H+/K+ ionophore, causing transmembrane pH and potassium gradients to be equilibrated. Despite the apparent lack of a BDQ-binding site, incorporating the E. coli Fo subunit into liposomes enhanced the ionophoric activity of BDQ. We discuss the possibility that localization of BDQ at F1Fo-ATP synthases enables BDQ to create an uncoupled microenvironment, by antiporting H+/K+ Ionophoric properties may be desirable in high-affinity antimicrobials targeting integral membrane proteins.
Pharmacology, Toxicology and Pharmaceutical Science
7
6%
Chemistry
7
6%
Other
9
7%
Unknown
43
35%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 64. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 December 2024.
All research outputs
#844,176
of 34,411,289 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#12,928
of 119,005 outputs
Outputs of similar age
#13,804
of 373,569 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#201
of 920 outputs
Altmetric has tracked 34,411,289 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 119,005 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 40.1. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 373,569 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 920 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.
