Abstract

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.

Highlights

  • The known antimicrobial effects of engineered silver nanoparticles (AgNPs), combined with increasing efficient production methods have contributed significantly to their prevalence in diverse consumer goods ranging from food items and packaging, to sporting equipment, clothing, water purification units and cosmetics [1,2,3]

  • Control treatment replicates showed no significant differences in the % CO2 fraction as compared to AgNPs (Figure 2) and AgMP-treatment groups

  • As a broad-spectrum low cost antibiotic, ampicillin is used orally to treat common infections and because of its utility, it has been placed on the list of essential medicines by the World Health Organization

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Summary

Introduction

The known antimicrobial effects of engineered silver nanoparticles (AgNPs), combined with increasing efficient production methods have contributed significantly to their prevalence in diverse consumer goods ranging from food items and packaging, to sporting equipment, clothing, water purification units and cosmetics [1,2,3]. Biofilms, which provide a refuge for Gram positive and negative bacteria, appear to be inhibited by AgNPs [11]. Taken together, these observations have helped foster the use of AgNPs for medical and personal health applications. These observations have helped foster the use of AgNPs for medical and personal health applications Even though these concentrations of AgNPs may not be directly toxic to human tissues, the efficacy of AgNPs against bacteria can result in shifts in bacterial consortia, which in turn could have an impact on host organisms [e.g. 12-14]. Community changes in response to these NPs have been noted in intestinal flora subsequent to oral ingestion in a range of species including fish, insects, and in a human model gut ecosystem [5,7,15]

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