# Plant-Derived Phytobiotics as Emerging Alternatives to Antibiotics Against Foodborne Pathogens
## 3 Mechanisms of Action of Phytobiotics Against Foodborne Pathogens
### Synergism Between Phytobiotics and Other Compounds  
When discussing the mechanisms of phytobiotic action, it is also important to highlight their synergistic effects, particularly in combination with antibiotics. The aforementioned mechanisms--such as disruption of cell wall or membrane integrity--often enhance bacterial susceptibility, making these structures more accessible to antibiotics, which frequently target them. Combining phytobiotics with antibiotics can enhance therapeutic efficacy or allow for reduced antibiotic dosages. A strong synergistic effect has been demonstrated, for instance, between berberine and antibiotics such as penicillin and erythromycin (101; 106). Furthermore, indole-based phytochemicals, including camalexin and brassinin, have been studied for their inhibitory effects on the AcrB efflux pump in _Escherichia coli_. Camalexin, in particular, significantly reduced the minimum inhibitory concentration (MIC) of antibiotics, confirming its potential as an antibiotic potentiator (125). Extracts from plants such as _Phylanthus emplica_ and _Allium sativum_ have shown synergistic effects with antibiotics such as ciprofloxacin and tetracycline, improving their efficacy against multidrug-resistant bacteria (162; 163). This is especially significant in the context of rising infections caused by multidrug-resistant pathogens. Similar synergistic effects have been observed with essential oils and plant extracts from _Syzygium aromaticum_, _Zingiber officinal_, and _Curcuma longa_, which increased the susceptibility of _Pseudomonas aeruginosa_ to chloroquine by inhibiting efflux pump activity (164). Likewise, essential oil and extracts from _Pilgerodendron wifterum_ effectively inhibited the NorA efflux pump in _Staphylococcus aureus_, thereby supporting antibiotic action (126). Propolis is another example of a natural compound with potent synergistic potential; when combined with antibiotics such as ciprofloxacin, erythromycincin, and gentamicin, it significantly enhanced their activity against _S. aureus_, mainly through inhibition of efflux pumps (165). The synergistic potential of phytobiotics can also be analyzed in the context of their combinations with other phytochemicals. Cooperative interactions between compounds have been observed in antimicrobial applications; for example, a combination of flavonoids and ellagitannins from _Cistus salwifolus_ extract significantly lowered the MIC against _S. aureus_(166). It is essential to emphasize that mechanisms such as membrane disruption or oxidative stress induction represent only a fraction of the biological effects exerted by phytobiotics. Due to their multifaceted nature and ability to target \begin{table}
\begin{tabular}{l l l} \hline \hline
**Mechanism** & **Mechanism of Action** & **References** \\ \hline  & Inhibition of protein synthesis (e.g., ribosomal binding) & [115; 140; 142] \\ \cline{2-3}  & Inhibition of DNA replication (e.g., DNA & \\  & gyrase, primase) & [135; 144; 145; 146] \\ \cline{2-3}  & Inhibition of protein & Inhibition of bacterial cell division (e.g., \\  & FtsZ inhibition) & [147] \\ \cline{2-3}  & Inhibition of translation-related proteins & [148] \\ \hline Induction of & & \\ oxidative stress & ROS induction and catalase inhibition & [149; 150; 151] \\ \hline Disruption of central & Disruption of central metabolism (glycolysis, & [148; 149] \\ \cline{2-3} metabolism & Inhibition of ATP synthase and & \\ by phytobiotics & H\({}^{+}\)-ATPase activity & [155; 156; 157] \\ \cline{2-3}  & Energy spilling and modulation of energy use & [158; 159; 160] \\ \hline \hline \end{tabular}
\end{table} 
Table 4: _Cont._numerous cellular processes simultaneously, phytobiotics exhibit significant therapeutic synergy [165; 166]. Their multi-target actions enhance the efficacy of combination therapies by modulating various signaling pathways [167]. In summary, all of the mechanisms described above--such as damage to bacterial membranes or increased oxidative stress--constitute only part of the broader spectrum of phytobiotic activity.