Synergistic Inhibitory Effect and Mechanism of Action of Cinnamaldehyde-Carvacrol Nanoemulsion on the Staphylococcus aureus and Escherichia coli Mixed Biofilms Formation.

The formation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) mixed biofilms challenges the treatment of bacterial infections. In this study, the synergistic effect of plant essential oils cinnamaldehyde (CA) and carvacrol (CV) on inhibiting S. aureus and E. coli mixed biofilms formation was investigated. The Q value of CA and CV combination on inhibiting mixed biofilms formation was 2.28, suggesting their synergistic effect. Furthermore, CA/CV nanoemulsion was prepared, which further enhanced the inhibitory effect. CA/CV nanoemulsion could significantly inhibit the mixed biofilms formation at 64 μg/mL by reduction of bacterial adhesion and motility, polysaccharide intercellular adhesin (PIA) synthesis, and the inhibition of LuxS/AI-2 expression. In the S. aureus and E. coli infected implant model of mice, CA/CV NEs demonstrated prominent inhibitory effect on the formation of S. aureus and E. coli biofilms, and simultaneously reduced the bacterial burden.