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

## TL;DR

European dewberry extracts show antibacterial activity against drug-resistant MRSA strains and could be a new therapeutic option.

## Contribution

This is the first study to demonstrate the antibacterial and biofilm-inhibiting effects of Rubus caesius extracts against MRSA and related staphylococci.

## Key findings

- Ethanolic and aqueous dewberry extracts inhibited biofilm formation in MRSA and MRCN strains by up to 100%.
- Extracts caused membrane depolarization in tested strains and acted synergistically with antibiotics like cefoxitin and amikacin.
- MIC values of antibiotics and extracts were significantly reduced when used in combination.

## Abstract

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 (LH2O, LEtOH) and stems (SH2O, SEtOH) against S. aureus and Staphylococcus epidermidis. The most active extracts were LEtOH (MIC 0.16 ± 0.40–1.56 ± 0.23 mg/mL) and LH2O (MIC 0.16 ± 0.20–10 mg/mL). The study showed that LEtOH, SEtOH and LH2O 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 LEtOH and SEtOH 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.