FIG 2.

Interspecies interactions between Pseudomonas aeruginosa and Staphylococcus aureus influence the efficacy of antibiotics against S. aureus biofilms. The P. aeruginosa-secreted molecule 2-heptyl-4-hydroxyquinolone N-oxide (HQNO) alters the sensitivity of biofilm-grown S. aureus to multiple antibacterial agents, including cell wall-targeting drugs (e.g., vancomycin), protein synthesis inhibitors (e.g., aminoglycosides), and membrane-active compounds (e.g., chloroxylenol). HQNO-mediated inhibition of the S. aureus electron transport chain (ETC) leads to slow growth and decreases the proton motive force (PMF), which promote tolerance to vancomycin and aminoglycosides, respectively. Additionally, exposure to HQNO increases the fluidity of the S. aureus cell membrane, enhancing the ability of the membrane-targeting antiseptic chloroxylenol (and other hydrophobic compounds) to eradicate S. aureus biofilms.