Antibacterial and antibiofilm efficacy of quercetin against <i>Pseudomonas aeruginosa</i> and methicillin resistant <i>Staphylococcus aureus</i> associated with ICU infections

Infections caused by multidrug-resistant pathogens, particularly in ICU settings, pose significant health risks globally. <i>Pseudomonas aeruginosa</i> (PA) and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) are prominent nosocomial pathogens among the ESKAPE group, known for their resistance mechanisms such as biofilm formation and quorum sensing. Quercetin, a flavonoid found in fruits and vegetables, exhibits diverse pharmacological properties, including antimicrobial activity. This study evaluated quercetin's efficacy against PA and MRSA through <i>in vitro</i> and <i>in vivo</i> experiments. Minimum Inhibitory Concentration (MIC) assays showed MIC values of 158 µg mL^-1 for PA and 176 µg mL^-1 for MRSA. Quercetin inhibited PA's swarming motility at concentrations as low as 39.5 µg mL^-1 and reduced MRSA viability in serum by up to 79%. Quercetin treatment significantly reduced biofilm formation by both pathogens, with <i>Pseudomonas aeruginosa</i> showing biomass reductions of 23% at 1/4 MIC (39.5 µg mL^-1) and 48% at 1/2 MIC, while methicillin-resistant <i>Staphylococcus aureus</i> exhibited reductions of 27% at 1/4 MIC and 53% at 1/2 MIC compared to the control. High-content fluorescence imaging demonstrated quercetin's ability to disrupt biofilm structure and viability. Moreover, quercetin suppressed EPS production and protease activity in both PA and MRSA, alongside downregulating virulence-related genes involved in quorum sensing and toxin production. <i>In vivo</i> studies using <i>Caenorhabditis elegans</i> confirmed quercetin's ability to reduce bacterial adherence and colonization. These findings underscore quercetin's potential as a therapeutic agent against multidrug-resistant pathogens in ICU settings, warranting further exploration for clinical applications.