Cuminaldehyde Potentiates the Antimicrobial and Antibiofilm Activity of Vancomycin: A Biochemical Study to Manage the Threats of Methicillin Resistant <i>Staphylococcus aureus</i> ( <scp>MRSA</scp> )

Methicillin-resistant Staphylococcus aureus (MRSA) is reported to cause serious health issues in humans by exploiting its biofilm network. To combat this global concern, the combined efficacy of cuminaldehyde (a bioactive phytochemical) and vancomycin (an antibiotic) was tested against MRSA strains. While both compounds exhibited independent antibacterial activity, their combination revealed improved efficacy against MRSA through additive interactions. Response surface methodology (RSM)-generated quadratic models optimized the combinatorial doses, revealing significant microbial growth inhibition of the MRSA strains (p < 0.05). Furthermore, the combined application of cuminaldehyde and vancomycin at sub-MIC doses could inhibit biofilm formation by lowering bacterial adhesion, extracellular polysaccharide (EP) synthesis and the extent of biofilm-associated proteins. Additionally, the mechanistic studies revealed that the said combination (cuminaldehyde and vancomycin) was found to accumulate oxidative stress with a ~2.5-fold increase in intracellular reactive oxygen species (ROS) and a ~2.3-fold reduction in membrane integrity. In view of the same, this combination attenuated key virulence factors (protease, hemolysin, and coagulase) and metabolic activity of MRSA. Hence, the combinations involving cuminaldehyde and vancomycin could potentially enhance the antimicrobial and antibiofilm efficacy, presenting a promising approach to combat the escalating crisis linked with MRSA-associated threats.