Gut-derived biofilm-forming bacteria as a source of catheter-associated infections: inhibitory effects of O-alkyl naringenin derivatives

The capacity for biofilm formation is a fundamental defense mechanism among antimicrobial-resistant pathogenic strains. In addition, its persistence may result in chronic colonization of host systems, and uncontrolled growth may lead to dangerous flow blockages, particularly in catheter-associated urinary tract infections. This warrants the search for novel anti-biofilm compounds to combat these pathogens. Naringenin is an example of such a structure, widely known for its multifunctional activity, targeting the synthesis of exopolysaccharide, the expression of biofilm-relevant genes, or efflux pump activity. In this study, we present a series of <i>O</i>-alkyl derivatives of naringenin and its oximes, that exhibited antimicrobial and biofilm-reducing activity against clinical strains of <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>, which are often the cause of urinary tract infections. Most of the derivatives were highly active against the planktonic form of bacteria, the most potent of them being 7-<i>O</i>-methylnaringenin oxime, diminishing the growth of <i>E. coli</i> and <i>S. aureus</i> by 43.2% and 74.6%, respectively. The initial screening of the antibiofilm capabilities of the derivatives was performed in static conditions in a gravimetric method utilizing quartz tuning forks. While most of them were significantly less active than against the planktonic form, the oximes of 7-<i>O</i>-methylnaringenin and 7-<i>O</i>-isopropylnaringenin were found to impair the growth of biofilm in case of both strains. Therefore, the observed reduction in biofilm mass under static conditions may reflect not only antimicrobial activity but also biofilm-specific mechanisms, as indicated by the use of flow conditions with catheters simulating urine flux. These studies confirmed the activity of 7-<i>O</i>-methylnaringenin oxime, which reduced <i>E. coli</i> CCM 5712 population.