Genome-Wide Bacterial Toxicity Screening Uncovers the Mechanisms of Toxicity of a Cationic Polystyrene Nanomaterial

Abstract

By exploiting a genome-wide collection of bacterial single-gene deletion mutants, we have studied the toxicological pathways of a 60-nm cationic (amino-functionalized) polystyrene nanomaterial (PS-NH(2)) in bacterial cells. The IC(50) of commercially available 60 nm PS-NH(2) was determined to be 158 μg/mL, the IC(5) is 108 μg/mL, and the IC(90) is 190 μg/mL for the parent E. coli strain of the gene deletion library. Over 4000 single nonessential gene deletion mutants of Escherichia coli were screened for the growth phenotype of each strain in the presence and absence of PS-NH(2). This revealed that genes clusters in the lipopolysaccharide biosynthetic pathway, outer membrane transport channels, ubiquinone biosynthetic pathways, flagellar movement, and DNA repair systems are all important to how this organism responds to cationic nanomaterials. These results, coupled with those from confirmatory assays described herein, suggest that the primary mechanisms of toxicity of the 60-nm PS-NH(2) nanomaterial in E. coli are destabilization of the outer membrane and production of reactive oxygen species. The methodology reported herein should prove generally useful for identifying pathways that are involved in how cells respond to a broad range of nanomaterials and for determining the mechanisms of cellular toxicity of different types of nanomaterials.

Considerations of Environmentally Relevant Test Conditions for Improved Evaluation of Ecological Hazards of Engineered Nanomaterials

“…69, 74, 75 Investigations include mechanistic gene transcriptional, 76-79 DNA damage, 80 metabolomics profiling, 81 and transgenerational 82, 83 experiments. Bottle-scale microcosms partially simulate limited levels of environmental complexity, 84 e.g.…”

Synthesis and characterization of monodispersed P(St-co-DMAEMA) nanoparticles as pH-sensitive drug delivery system

“…The reasons for choosing styrene as the co-monomer are as follows: firstly, styrene has strong tendency to co-polymerize with DMAEMA rather than with itself (reactivity ratio of styrene is lower than 1 in the mixture of water and 2-butanone [28,29]). Secondly, polystyrene is a kind of material with low cell toxicity [30,31] and commercial availability.…”

Comparative and Mechanistic Genotoxicity Assessment of Nanomaterials via a Quantitative Toxicogenomics Approach across Multiple Species

“…1 Nanomaterial-induced toxicity has been observed in human and other lives via mechanisms related to oxidative stress, 2 inflammatory response, 3−5 protein binding, 6 ion influx disturbance, 7 and dissolution and release of toxic ions. It is currently accepted that oxidative stress and inflammation are the major mechanisms of nanotoxicity.…”