## 4 Discussion  
The probiotic _Bacilli_, for instance, _L. plantarum_ may produce and secrete a myriad of volatile compounds and secondary metabolites in the vicinity of its existence that often exhibits antibacterial or antifungal activities [36]. The cell-free supernatants from _L. plantarum_ have been shown to inhibit several pathogenic microbes [40; 41]. Some of them could prevent the formation of pathogen biofilms [40; 42]. In this study, we assessed the antagonistic activity of the cell-free postbiotics from _L. plantarum_ colonies against bacterial and yeast pathogens. The tested postbiotics did not exert notable bacteriostatic and fungistatic activities, but drastically affected the biofilms of the tested pathogens. Studies have shown that _L. plantarum_ LR/14 exhibited profound anti-_Candida_ activity [43]. Here, we show for the first time that the postbiotics (intracellular and extracellular secretions) from _L. plantarum_ colonies exhibit antibiofilm and anti-hyphal activities without affecting the growth of planktonic counterparts (Figure S1 and 4a). It is conceivable that the concentrations of the metabolites in the cell-free postbiotics are substantially low. That said, our findings demonstrate an antibioofilm effect displayed by the postbiotics, which is a promising alternative for antimicrobial approaches. Next, we addressed the anti-hyphal activities of the culture filtrates. The Y-H switching is a dimorphic trait by which _C. albicans_ helps to manifest its pathogenicity [29]. The hyphal mode represents the aggressive phase of _C. albicans_ infection. In humans, hyphae induce tissue damage by an invasion of epithelial cells, causing cytolysis or cell death [44]. In laboratory models such as _C. elegans_, _C. albicans_ hyphae pierce through nematode cuticles that progressively kill them [45; 46]. _C. albicans_ virulence can be alleviated if the hyphae are degraded or neutralized. Several studies are focused on screening chemicals/natural products, synthesizing newer drugs, or repurposing drugs to degrade hyphae or, at a minimum, to prevent Y-H transition [29; 47]. The tested postbiotics in this study prevented hyphal filamentations in liquid RPMI and on hard agar, indicating that the postbiotics contain chemicals that function as anti-hyphal agents. Separately, we also identified methyl-2-ketones, 2-undecanone, secreted from 7-day _L. plantarum_ colonies by GC-MS profiling (Figure S5). A recent study revealed that methyl-2-ketones were the active volatile chemicals in essential oils (EO) of _Ruta gravelens_ and _R. caloleensis_ plants that showed profound anti-_C. albicans_ activity [48; 49]. Furthermore, ketoacids such as nonanoic acid and heptanoic acid were reported to show anti-hyphal and antibioofilm activities against _C. albicans_[50]. The methyl-2-ketones might also account for anti-_Candida_ and antibacterial activities. One of the ketones, 2-undecanone, was effective in controlling Y-H transitions and in preventing biofilm formations in _C. albicans_. Studies have shown that blocking Hwp-1 can prevent biofilm formation [20; 39]. Recently, the molecular interaction of a natural product, morin, was assessed against the Hwp-1. The study revealed a tight binding interaction of morin with the active site of Hwp-1 facilitated by a hydrogen bonding with Gln amino acid residue [20]. In our model, 2-undecanone interacted with Hwp-1 active sites and formed a hydrogen bonding with Gln 58 amino acid residue. Interestingly, other ketones (2-nonanone and 2-heptanone) did not form any hydrogen bonds, thus confirming the importance of the Gln hydrogen bond in maintaining tight ligand-protein interactions that govern the inactivity of the protein. The docking results rationalize the biofilm inhibitory activity of 2-undecanone and partially confirm that the ketone interacts with Hwp-1, and inactivates its function, consequently preventing biofilm inhibition by _C. albicans_.