Staphylococcus aureus is a gram-positive pathogen responsible for a variety of difficult to treat infections. Antibiotic tolerance of S. aureus is a serious problem and is associated with treatment failure, particularly in biofilm-associated infections. Persister cells are antibiotic tolerant phenotypic variants capable of surviving high doses of bactericidal antibiotics for long periods of time. We find that population level tolerance and the tolerance of persister sub-populations can be explained by a drop in the energy currency of the cell, ATP. Furthermore, we have previously shown that the ATP-independent antibiotic, ADEP4, which turns the ClpP peptidase into a non-specific protease can kill persisters and eradicate bacterial populations.