title: 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.
authors.affiliation: University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Ivask
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Suarez
authors.forename: Trina
authors.initials: T
authors.lastname: Patel
authors.forename: David
authors.initials: D
authors.lastname: Boren
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.forename: Patricia
authors.initials: P
authors.lastname: Holden
authors.forename: Donatello
authors.initials: D
authors.lastname: Telesca
authors.forename: Robert
authors.initials: R
authors.lastname: Damoiseaux
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Bradley
authors.forename: Hilary
authors.initials: H
authors.lastname: Godwin
mesh_terms: D000588:Amines / Q000737:chemistry / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D017353:Gene Deletion; D016680:Genome, Bacterial / Q000187:drug effects*; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D011137:Polystyrenes / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000588:Amines; D011137:Polystyrenes; D017382:Reactive Oxygen Species