Repurposing ibuprofen to control Staphylococcus aureus biofilms.

Drug repurposing arises as an interesting alternative to overcome the limited efficacy of current available antibiotics by reducing time, cost and risk associated with drug innovation. In this study, the activity of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), was evaluated on the control of pre-established adhered cells (2 h) and 24 h old biofilms of Staphylococcus aureus. Bacterial adhesion was performed by S. aureus CECT 976, while biofilm formation was also performed by the antibiotic-resistant strains: SA1199B, RN4220 and XU212. The treatment with ibuprofen promoted metabolic reductions up to 80% and total loss of culturability of adhered cells and 24 h old biofilms. Ibuprofen demonstrated moderate efficacy to remove biofilms of S. aureus CECT 976 (removal ≤ 40%), but did not display removal action against the antibiotic-resistant strains. Antibacterial activity (inhibitory and bactericidal) and mode of action of ibuprofen were also assessed using different bacterial physiological indices. Minimum inhibitory and bactericidal concentrations of the four S. aureus strains ranged between 500 and 2000 mg L-1 and 1400 - >2000 mg L-1, respectively. After S. aureus CECT 976 incubation with ibuprofen, cell permeation to propidium iodide, release of intracellular potassium and changes on cell surface hydrophobicity were observed. The overall results, demonstrate that ibuprofen can control S. aureus planktonic and sessile growth, with strong destabilizing and disrupting action on the cytoplasmic membrane.