## 4 Discussion
However, the interaction of caffeic acid with antibiotics (erythromycin, clindamycin, and cefoxitin) increased the antibacterial activity of the antibiotic-phenol combination [44; 48]. The initial caffeic acid has been shown to exhibit antimicrobial activity against methicillin-sensitive _Staphylococcus aureus_ (MSSA) and methicillin-resistant _Staphylococcus aureus_ (MRSA) strains, and the mechanism of CA action is related to cell membrane damage and changes in the oxygen metabolism of _S. aureus_ cells [49]. This polyphenic compound is characterized by strong nucleophilic properties, which enable it to donate electron pairs to electrophilic functional groups of proteins and lipids in the cell membrane, leading to dysfunction of this membrane and inhibiting \(\upalpha\)-hemolysin secretion by _S. aureus_. Studies of the antimicrobial activity of CA, EDHB, and catechhin hydrate (CH) showed that caffeic acid exhibited stronger antitumor activity than EDHB and CH and a greater synergistic effect with antibiotics than the compounds. The high antimicrobial activity of caffeic acid is due to a propene side chain, which reduces its polarity compared to the hydroxybenzoic structure of protocatechic acid [50]. The authors of the work [51] evaluated the antibacterial activity of extracts obtained from sugarcane bagasse. The main components of the obtained extracts were phenolic acids, such as gallic acid, ferulic acid, coumaric acid, and chlorogenic acid. The tested extracts were characterized by antibacterial activity against _S. aureus_ strains (MIC = 0.625 mg/mL) [51]. The study of plant extracts' antibacterial activity has been focused so far. The antibacterial activity of bio-ferments obtained by the fermentation of pomace, extract, cold-pressedoil, and seeds from milk thistles containing polyphenic compounds, among others, has not been analyzed. Therefore, preliminary studies were carried out in the present study to evaluate the antibacterial activity of new bio-ferments. The presence of phenolic hydroxyl groups in the structure of polyphenols makes them have a high affinity for binding to proteins and lipids in the cell membrane [52]. As a result, phenolic compounds contained in bio-ferments can inhibit microbial enzymes and, at the same time, increase their affinity for cytoplasmic membranes, thus increasing antimicrobial activity against the strains tested. The present study demonstrates that bio-ferments containing polyphenols are a promising source of effective, safe, and inexpensive antimicrobial compounds. The antimicrobial potential of fermented plant materials opens up a wide range of possibilities for new antimicrobial therapies. Because the bio-ferments had higher MIC values than antibiotics, they cannot be used in antimicrobial monotherapy due to their insufficient therapeutic effect. The antimicrobial activity of the tested bio-ferments was established at the following levels: moderate (B-S and B-P) or weak (B-E and B-O). However, implementing combination therapy with antibiotics can improve their pharmacokinetic and pharmacodynamic properties and reduce the dose of antibiotic intake. Studies by other authors have shown that the strain of _Staphylococcus aureus_ was sensitive to most of the drugs used and resistant to doxycycline (MIC = 32 ug/mL) and florfenicol (MIC = 64 ug/mL) [53; 54]. _Escherichia coli_ was susceptible to ceftour (MIC = 0.125 ug/mL), kanamycin (MIC = 2 ug/mL), colistin sulfate (MIC = 0.125 ug/mL), florfenicol (MIC = 2 ug/mL), and rifampicin (MIC = 4 ug/mL), while resistant to amoxicillin and doxycycline (MIC = 32 ug/MG), acetylisovaleryltylosin tartrate (MIC = 128 ug/mL), sulfadimidine and enrofloxacin (MIC = 16 ug/mL), and limomycin (MIC = 512 ug/mL) [53; 55]. The MIC values of the antibiotics against _Pseudomonas aeruginosa_ ATCC 27853 were within the CISI accuracy range throughout those studies: ceftazidine (MIC = 1-4 mg/L), tobamycin (MIC = 0.25-16 mg/L), piperacillin (MIC = 4-128 mg/L), ciprofloxacin, and colistin (MIC = 0.25-2 mg/L) [56; 57].