ubunit.
A second successful example of an antibiotic targeting an ATPdependent
bacterial enzyme is bedaquiline, a diarylquinoline identi-
fied in a screening campaign for molecules that could kill M.
tuberculosis.
199 The mechanism of action was determined by
generation of resistant mutants and mapping them by wholegenome
sequencing, allowing identification of the Fo subunit of the
Mtb ATP synthase.200,201 The molecule is specific for mycobacterial
ATP synthase202 and has proven efficacy through phase II trials,199,203
with a new drug application filed in July 2012 and approval granted at
the start of 2013.45 Perhaps there are still more ATP-utilizing proteins
within the Mtb proteome that might surface as valid therapeutic
targets.204