# Plant-Derived Phytobiotics as Emerging Alternatives to Antibiotics Against Foodborne Pathogens
## 3 Mechanisms of Action of Phytobiotics Against Foodborne Pathogens
### Disruption of Bacterial Cell Wall Integrity, Membrane Structure, and Biofilm Formation
Phenolic compounds and alkaloids from various plants inhibit the activity of peptidoglycan synthases, thereby preventing proper bacterial cell wall formation [115]. One key target is the MurA enzyme, which catalyzes the first step in peptidoglycan biosynthesis. Inhibition of MurA disrupts the structural integrity of the cell wall, ultimately leading to cell lysis [116; 117]. Compounds such as catechin (derived from _Uncaria gambitr_) and allypyrocatechol (_Piper betle_) have been shown to bind directly to MurA and inhibit its enzymatic activity, as demonstrated in both in vitro and in silico studies [116; 117]. Autolysins--enzymes responsible for controlled degradation of peptidoglycan--may also be targets of phytobiotic modulation. Studies have shown that LytC and LytF autolysins alter their dynamics and subcellular localization in response to environmental cues or the presence of inhibitors, suggesting a potential regulatory effect by phytobiotics [118]. Moreover, certain plant-derived compounds, such as phytobiotics isolated from traditional Chinese medicines, have been shown to inhibit sortase A, the enzyme responsible for anchoring surface proteins to the cell wall in Gram-positive bacteria. Inhibition of this enzyme reduces bacterial adhesion and virulence [119]. Through interference with various components or stages of cell wall synthesis, phytobiotics can weaken the structural integrity of bacterial walls, increase susceptibility to environmental stress, and ultimately lead to bacterial cell death. Phytobiotics may also alter the chemical and functional composition of bacterial cell walls by modifying key components and inhibiting enzymes involved in their biosynthesis. Exposure to these compounds can lead to significant deformation of the cell wall, resulting in changes in cell shape and size. For example, cranberry juice has been shown to modify the morphology of _E. coli_, affecting the expression of flagellar proteins and reducing the fimbrial structures such as P fimbiae [120]. Similarly, an extract from _Pelargonium zonale_ induced morphological abnormalities in _Candida albicans_, including cell wall damage and aberrant budding [121]. Phytobiotics also show potential as efflux pump inhibitors. Efflux pumps are often associated with the development of antibiotic resistance in bacteria. These transport systems actively excrete a wide range of antibiotics and other toxic compounds from bacterial cells, reducing intracellular concentrations and diminishing treatment efficacy [122]. Natural compounds may enhance the efficacy of antibiotics by inhibiting efflux pump activity, thereby increasing intracellular antibiotic concentrations [122; 123; 124; 125; 126]. For example, the ethyl acetate fraction of pomeranate (_Punica granatum_) exhibited potent efflux pump inhibitory activity [127]. Flavonoids such as phloretin and naringenin, when combined with existing efflux pump inhibitors, enhanced the antibacterial activity against _Pectobacterium brasiliense_[128]. However, exposure to phytobiotics may also drive adaptive responses. Under phytobiotic-induced stress conditions, bacteria can adopt filamentous morphology as a survival strategy. This adaptation promotes biofilm formation, which in turn increases resistance to antimicrobial agents [129; 130]. Biofilms represent a crucial bacterial adaptation to environmental stressors, including the action of phytobiotics. These structures, composed of bacterial cells embedded in an extracellular matrix, significantly restrict the penetration of antimicrobial agents and thus enhance microbial survival. Certain phytobiotics affect biofilm development. For instance, plant extracts from the genus _Inula_ significantly reduced biofilm biomass and altered colony morphology of _Chromobacterium violaceum_, indicating disruption of biofilm structural organization [131]. This control over biofilm formation is closely linked to interference with quorum-sensing mechanisms.