Differential modulation of gentamicin antibacterial activity by vitamin B12 and vitamin D3 against Gram-positive and Gram-negative bacteria: an in vitro–in silico study
Year: 2026
Type: article
Abstract: Introduction Antimicrobial resistance and gentamicin-associated toxicity necessitate the development of non-antibiotic adjuvants that enhance aminoglycoside efficacy while reducing required doses. Vitamins B12 and D3 possess physicochemical and biological properties that may influence bacterial resistance pathways. This study aimed to evaluate the modulatory effects of these vitamins on gentamicin against representative bacterial strains using an integrated in vitro–in silico approach.Materials and methods Eight ATCC Gram-negative and Gram-positive reference strains were evaluated. Antibacterial activity was assessed using agar disk diffusion and broth microdilution assays to determine inhibition zones, minimum inhibitory concentrations (MICs), and MIC fold reduction (MFR). In silico analyses targeted the 30S ribosomal subunit, a cobalamin riboswitch, and a proton motive force (PMF)-related protein to explore mechanistic interactions underlying observed phenotypes.Results Vitamin B12 significantly enhanced gentamicin efficacy, reducing MICs by up to 8-fold and demonstrating synergistic activity (MFR ≥ 4) against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis. Conversely, vitamin D3 displayed antagonistic effects (MFR ≤ 0.5) in several Gram-positive strains, increasing gentamicin MICs by up to 16-fold. Computational results indicated cooperative stabilization of gentamicin at the ribosomal target and increased affinity for the cobalamin riboswitch in the presence of vitamin B12, whereas vitamin D3 showed strong binding to a PMF-related protein, consistent with impaired aminoglycoside uptake.Conclusion Vitamin B12 represents a promising dose-sparing adjuvant for gentamicin, while vitamin D3 may compromise aminoglycoside efficacy under the tested conditions. These findings warrant further validation using clinical isolates and biofilm models before considering vitamin-based strategies in aminoglycoside stewardship.
Source: Annals of Medicine
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,557
OpenAlex ID: W7155715212