Comprehensive in silico and in vitro analysis of Lactobacillus sp. based secretory proteins and quorum-sensing peptides as potential antibiofilm bioactive agents against Streptococcus mutans

Human oral cavity is a habitat for diverse microbiomes that are influenced by an individual’s hygiene, diet, genetics, and environmental conditions. Dental caries is a prevalent disease caused by dysbiosis of the oral microbiome, which is commonly influenced by the cariogenic pathogen Streptococcus mutans, a strongly biofilm-forming and acid-producing bacterium. Probiotic Lactobacillus species have beneficial effects against several oral pathogens by secreting extracellular products that inhibit their growth. The current study applies a sequence of in silico and in vitro methods to target Streptococcus mutans biofilms or virulence factors via the secretory proteins and quorum-sensing peptides of Lacticaseibacillus rhamnosus . The antibacterial assay and antibiofilm activity revealed a substantial impact of L. rhamnosus cell-free supernatant (CFS) and purified proteins on bacterial growth and biofilm biomass. Computational biology prediction with genomic data and liquid chromatography tandem mass spectrometry (LC MS/MS) for identification of candidate peptides revealed 14 secretory proteins with an individual count of 62 unique peptides. The anticipated optimal bioactive potential of extracellular secretory proteins and bioactive peptides for antibiofilm and quorum-sensing disruption was assessed. Molecular docking and molecular dynamics analyses revealed that the potential bioactive peptide LRHA_PEP33 interacted sufficiently with major virulence factors, such as DexA, GtfC, GtfD, GtfB, VicK, and GbpB, indicating that LRHA_PEP33 may interfere with biofilm-associated proteins. Our studies have successfully determined the structural- and molecular-level interactions of probiotic secretory proteins and quorum-sensing peptides, which target pathogenic virulence factors of Streptococcus mutans . In conclusion, our research offers promise for a new, precisely targeted therapeutic approach against cariogenic biofilms and the restoration of oral microbial harmony.