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Interaction between a Broad-spectrum Antibiotic and Silver Nanoparticles in a Human Gut Ecosystem

Pranab Das, Saulnier E, Carlucci C, Allen-Vercoe E, Shah V and Virginia K Walker

The antimicrobial properties of engineered silver nanoparticles (AgNPs) have led to their wide use in diverse consumer products. Ampicillin too, acts as a broad-spectrum antibiotic and thus is prescribed for the treatment of many common infections, but with the problematic emergence of ampicillin-resistant bacteria. As a consequence, there has been some interest in the combination of these two distinct chemistries prompted by the clinical challenge of resistance. Prior to trials of combination therapy, however, it is important to understand the impact on human microbiomes. Here we investigated the effect of ampicillin and AgNPs, both individually and in a combined therapy on a human intestinal ecosystem known as a defined experimental community (DEC-60). The DEC-60 consortia was co-treated with a concentration of AgNPs (50 mg/L) known to have a minimal impact, and a broad range of the antibiotic up to the clinical dose (6 mg/L). The addition of AgNPs to sub-clinical doses of ampicillin (0.06 and 0.6 mg/L) had a significantly impact (p<0.001-0.05) on gas production (%CO2 and %N2) and changed the composition of fatty acid methyl ester signatures so that they were distinct from each individual antimicrobial, as well as un-treated control cultures. DNA sequencing, supported by multidimensional scaling analysis, confirmed the community shift and showed distinct phylogenetic distributions at different concentrations of ampicillin, depending on the presence of AgNPs. Together, these results suggest that the antibacterial efficacy of sub-clinical doses of ampicillin was increased by AgNPs, possibly due to the synergistic effect of damage to the bacterial cell walls. Not only does this analysis provide insight into AgNP toxicity, it offers some promise that combined antimicrobial therapies may have value in a clinical setting.

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