<i>In silico</i> analysis of bacteriocins from <i>Lactobacillus acidophilus</i> membrane vesicles against <i>Streptococcus mutans</i> GtfB protein

Oral pathogens pose a significant global health concern, affecting 80% of the world's population across all age groups. Among these pathogens, <i>Streptococcus mutans</i> stands out as a prominent threat. The rise in antibiotic resistance has limited the effectiveness of conventional antibiotics. In contrast, probiotics produce antibacterial peptides known as bacteriocins, which exhibit inhibitory effects against closely related and even unrelated bacterial species. Specifically, <i>Lactobacillus acidophilus</i> bacteriocins are encapsulated within membrane vesicles (MVs), allowing for long-distance transport and targeted delivery. However, no prior studies have investigated <i>L. acidophilus</i> membrane MV-encapsulated bacteriocins against <i>S. mutans</i>. In this study, we employed in-silico methods to target bacteriocins from MVs of <i>L. acidophilus</i>, against the GtfB virulence protein of <i>S. mutans</i>. Our findings indicate that Lactacin B exhibits non-toxic, non-antigenic, and non-hemolytic properties, making it a promising bioactive peptide candidate. Notably, Lactacin B forms strong interactions with GtfB in the active site, with a binding energy of -15.1 kcal/mol and four hydrogen bonds. MD simulations for 100 ns and MMPBSA assays of the complex further support the efficient binding. The fluctuation of RMSD and RMSF is minimal and corresponds to greater stability of the complex. Lactacin B interaction with gtfB mightreduce GtfB's virulence potential, and hinder <i>S. mutans</i> adhesion to oral surfaces, subsequently mitigating biofilm formation and preventing dental caries. However, additional <i>in vitro</i> studies are necessary to validate these findings.