Rubus caesius L. (European Dewberry) Extracts as a Novel Therapeutic Strategy Against MRSA Strains

Increased bacterial resistance to current antibiotics leads to a depletion of therapeutic options in medicine. One of the problems of current therapy is methicillin-resistant Staphylococcus aureus (MRSA), which, in addition to resistance to β-lactam antibiotics, is multidrug-resistant. Some strains can also produce biofilms, a multicellular structure that is resistant or tolerant to various antibiotics. In hospitals worldwide, about 15% of invasive infections are caused by MRSA. Extracts of Rubus caesius (dewberry) contain high concentrations of compounds such as phenolic acids, flavonoids, tannins, and anthocyanins, which have potential antibacterial properties. This study is the first to demonstrate the activity of aqueous and ethanolic extracts of dewberry leaves (L_H2O, L_EtOH) and stems (S_H2O, S_EtOH) against S. aureus and Staphylococcus epidermidis. The most active extracts were L_EtOH (MIC 0.16 ± 0.40-1.56 ± 0.23 mg/mL) and L_H2O (MIC 0.16 ± 0.20-10 mg/mL). The study showed that L_EtOH, S_EtOH and L_H2O extracts inhibited biofilm formation by clinical strains MRCN (methicillin-resistant coagulase-negative staphylococci) and MRSA (biofilm biomass reduction from 40 to 100%). Furthermore, 3,3'-dipropylthiacarbocyanine (DiSC₃(5)) and N-phenyl-naphthylamine (NPN) were used to show that L_EtOH and S_EtOH caused the membrane depolarization of the strains studied. We also showed that the extracts acted synergistically and additively with cefoxitin and amikacin, reducing the MIC values of the antibiotics used by 8- to 16-fold and of the extracts tested by 4- to 8-fold. This study provides new data on potential antibacterial drugs of therapeutic importance.