Differential modulation of gentamicin antibacterial activity by vitamin B12 and vitamin D3 against Gram-positive and Gram-negative bacteria: an <i>in vitro-in silico</i> study.
Vitamin B12 may enhance gentamicin's effectiveness, while vitamin D3 could reduce it, indicating a need for careful consideration in aminoglycoside therapy.
Where it sits
this study against the rest of the kpv corpusSummary and findings
This study evaluated the effects of vitamins B12 and D3 on the antibacterial activity of gentamicin against various bacterial strains. Vitamin B12 enhanced gentamicin efficacy, while vitamin D3 reduced its effectiveness. The findings suggest potential roles for these vitamins in aminoglycoside therapy.
Abstract
<h4>Introduction</h4>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 <i>in vitro</i>-<i>in silico</i> approach.<h4>Materials and methods</h4>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). <i>In silico</i> analyses targeted the 30S ribosomal subunit, a cobalamin riboswitch, and a proton motive force (PMF)-related protein to explore mechanistic interactions underlying observed phenotypes.<h4>Results</h4>Vitamin B12 significantly enhanced gentamicin efficacy, reducing MICs by up to 8-fold and demonstrating synergistic activity (MFR ≥ 4) against <i>Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis</i>. 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.<h4>Conclusion</h4>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.
Background
The study addresses the challenge of antimicrobial resistance and the toxicity associated with gentamicin, an aminoglycoside antibiotic. Previous research has indicated that non-antibiotic adjuvants may enhance antibiotic efficacy while reducing dosage requirements. This study is significant as it explores the potential of vitamins B12 and D3 to modulate the effectiveness of gentamicin against both Gram-positive and Gram-negative bacteria.
Methods
The study utilized an integrated in vitro-in silico approach, evaluating eight ATCC Gram-negative and Gram-positive reference strains. Antibacterial activity was assessed through agar disk diffusion and broth microdilution assays, measuring inhibition zones, minimum inhibitory concentrations (MICs), and MIC fold reduction (MFR). The study did not specify the exact n or duration of the experiments.
Results
Vitamin B12 significantly enhanced gentamicin efficacy, reducing MICs by up to 8-fold, while vitamin D3 increased gentamicin MICs by up to 16-fold in several Gram-positive strains. The study reported MFR values, with vitamin B12 showing synergistic activity (MFR ≥ 4) and vitamin D3 exhibiting antagonistic effects (MFR ≤ 0.5).
Interpretation
The findings suggest that vitamin B12 may serve as a promising adjuvant to enhance gentamicin's antibacterial activity, which aligns with previous literature on non-antibiotic adjuvants. However, the clinical significance of the observed effects remains uncertain, particularly given the small effect sizes and the in vitro nature of the study. Confounding factors include the lack of human data and the need for further validation in clinical settings.
Key findings
- Vitamin B12 reduced MICs by up to 8-fold against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis.
- Vitamin D3 increased gentamicin MICs by up to 16-fold in several Gram-positive strains.
- Vitamin B12 demonstrated synergistic activity with MFR ≥ 4.
- Vitamin D3 displayed antagonistic effects with MFR ≤ 0.5.
Limitations
- In vitro study, results may not translate to clinical settings.
- No human data provided.
- Small sample size of bacterial strains evaluated.
- Short duration of study not specified.