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

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• 作者：Angela Ivask ; Elizabeth Suarez ; Trina Patel ; David Boren ; Zhaoxia Ji ; Patricia Holden ; Donatello Telesca ; Robert Damoiseaux ; Kenneth A. Bradley ; Hilary Godwin
• 刊名：Environmental Science & Technology (ES&T)
• 出版年：2012
• 出版时间：February 21, 2012
• 年：2012
• 卷：46
• 期：4
• 页码：2398-2405
• 全文大小：365K
• 年卷期：v.46,no.4(February 21, 2012)
• ISSN：1520-5851

文摘

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-NH₂) in bacterial cells. The IC₅₀ of commercially available 60 nm PS-NH₂ was determined to be 158 渭g/mL, the IC₅ is 108 渭g/mL, and the IC₉₀ is 190 渭g/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-NH₂. 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-NH₂ 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.