A molecular biological model describing silver nanoparticle mechanism of toxicity and associated antibiotic resistance
Creators: name: Chambers, Bryant Allson
name: 0000-0002-2233-3207
Publisher: name: The University of Texas at Austin
Year: 2018
Subjects: Antibiotic resistance
Silver nanoparticles

description: Control of microbial growth is key to proper function of engineered systems and human health. Combating biological contamination in engineered processes is complicated due to the limited number of materials that are both able to impede microbial growth and are benign with respect to human and environmental health. Silver nanoparticles (AgNPs) have emerged as a novel biocide, reducing biological fouling in consumer goods and health care materials. Their almost ubiquitous usage is primarily due to their microbial cytotoxicity, limited human toxicity, and their ability to be incorporated into a wide variety of materials. The use of AgNPs is not without challenges; microbial toxicity varies by exposure methodology, and studies have shown that AgNPs have the potential to disrupt engineered biological processes either as nanoparticles or through the dissolution of aqueous silver (Ag([subscript aq])). The use of AgNPs is further complicated by their mechanisms of action; there is significant overlap of their biological targets with the targets of antibiotics. Thus, antibiotic resistance might result from AgNP exposure through the processes of co- and cross-resistance, in which one chemical selects for microbial resistance to a second (unrelated) chemical. In this work, the impact of AgNP aggregation and dissolution on toxicity to Escherichia coli was examined. Data indicate that conditions promoting high fractal dimension promote greater toxicity and induce an oxidative stress response. Subsequent studies on the opportunistic human pathogen Pseudomonas aeruginosa were directed at elucidating the mechanisms of action of AgNPs and the microbial response. Transcriptomic and proteomic studies focused on defining a model of bacterial AgNP interaction and isolated mechanisms of toxicity of AgNPs. Further these data provided the first evidence of AgNP exposure resulting in antibiotic resistance through the expression of multidrug efflux pumps. Transcriptomic data indicated that the stress response systems activated as a result of AgNP exposure were localized to the periplasm while the stress response systems activated as a result of Ag([subscript aq]) exposure were localized to the cytoplasm, which supports a surface attachment model of bacterial AgNP interaction distinct from that of Ag([subscript aq]). Transcriptomic studies revealed that key antibiotic resistance systems, including mexGHI and mexPQ, were stimulated by AgNP exposure. P. aeruginosa cells that were pre-exposed to a sublethal concentration of AgNPs demonstrated increased resistance in subsequent antibiotic challenges, demonstrating that antibiotic resistance can be induced by AgNPs. The findings of this study are an important contribution to our understanding of the impacts of co- and cross-resistance induced by AgNP exposure and will ultimately help inform decisions related to human and environmental health