The in vitro studies combined with molecular docking and MM-GBSA binding free energy calculations reveal broad-spectrum antibacterial activity of bacteriocin from curd-derived Limosilactobacillus fermentum with probiotic attributes

• Published in: In Silico Research in Biomedicine Vol. 1; p. 100009
• Main Authors: Halder, Debashis, Mandal, Shyamapada
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2025
• Subjects: Antibacterial activity; Bacteriocin; Lactobacillus fermentum; MM-GBSA binding free energy; Molecular docking; Probiotic property; Antibacterial activity; Lactobacillus fermentum; Probiotic property; Molecular docking; MM-GBSA binding free energy; Bacteriocin
• ISSN: 3050-7871
• DOI: 10.1016/j.insi.2025.100009

•Limosilactobacillus fermentum from cured showed favourable probiotic attributes•Bacteriocin from L. fermentum displayed broad-spectrum antibacterial properties•L. fermentum bacteriocin binds with virulence proteins sortase A and exotoxin A•MM-GBSA analysis conformed the stability of protein-bacteriocin docked complexes•Bacteriocin from probiotics is useful in peptide-based antibacterial drug discovery Bacteriocin derived from probiotics are well-known antibacterial agents. We validated the probiotic qualities of a curd-derived Lactobacillus fermentum (=Limosilactobacillus fermentum) LMEM22 strain, performed safety profiling, confirmed molecular identity, and accomplished in vitro antibacterial activity analysis of bacteriocin combined with molecular docking. The curd isolate of L. fermentum LMEM22, as identified through 16S rRNA gene sequencing and phylogeny analysis, showed probiotic features and acceptable safety profiles by in vitro methods. The bacteriocin isolated from L. fermentum LMEM22 displayed antibacterial activity against gram-negative (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella enterica serovar Typhi and Proteus vulgaris) and gram-positive (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus and Listeria monocytogenes) bacteria with ZDI (zone diameter of inhibition) of 17 – 24 mm and minimum inhibitory concentration (MIC) value of 41 – 199 µg/ml. Molecular docking demonstrated the inhibition capacity of L. fermentum bacteriocin against sortase A from Staphylococcus aureus and exotoxin A from Pseudomonas aeruginosa. The protein-bacteriocin complex energetic stability was confirmed by MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energy calculation. Combined with molecular docking and MM-GBSA binding free energy calculations, in vitro studies established the broad-spectrum antibacterial activity of Limosilactobacillus fermentum bacteriocin, thus recommending the application of bacteriocin in food and medicine, subject to further clinical experiments. [Display omitted]