Biofilm Control Activity of Triphenylphosphonium‐Conjugated Curcumin Against Staphylococcus aureus

ABSTRACT Hospital‐ and community‐acquired Staphylococcus aureus infections are dominated by their biofilms and cause difficult‐to‐treat persistent infections. As an alternative anti‐biofilm agent, the efficacy of triphenylphosphonium (TPP)‐conjugated curcumin (TPP‐curcumin) was determined against S. aureus biofilms in comparison to that of curcumin and commercial antibiotics. TPP‐curcumin elicited strong anti‐staphylococcal activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 3.125 and 6.25 μM, respectively. The MIC and MBC values for curcumin and ampicillin were > 125 and > 286.2 μM (100 μg/mL), respectively. The MIC and MBC values were 25.7 μM (12.5 μg/mL) and 103 μM (50 μg/mL), respectively, for kanamycin. TPP‐curcumin was multi‐fold more effective than curcumin in inhibiting biofilm growth. Minimum biofilm inhibitory concentration (MBIC) values of TPP‐curcumin, curcumin, ampicillin and kanamycin were 3.125, > 125, > 286 and 25 μM, respectively. Besides inhibiting biofilm formation, TPP‐curcumin has effectively killed S. aureus cells in pre‐formed or established biofilms. Treatment of biofilms with 25 μM TPP‐curcumin achieved near‐complete cell killing. Exposure to TPP‐curcumin led to severe membrane damage and oxidative stress in S. aureus cells. The strong antimicrobial and antibiofilm activity of TPP‐curcumin suggests its potential use for developing or augmenting antibacterial therapies for drug‐resistant S. aureus infections.