title: Cu Nanoparticles Have Different Impacts in Escherichia coli and Lactobacillus brevis than Their Microsized and Ionic Analogues.
abstract: Copper formulations have been used for decades for antimicrobial and antifouling applications. With the development of nanoformulations of copper that are more effective than their ionic and microsized analogues, a key regulatory question is whether these materials should be treated as new or existing materials. To address this issue, here we compare the magnitude and mechanisms of toxicity of a series of Cu species (at concentration ranging from 2 to 250 μg/mL), including nano Cu, nano CuO, nano Cu(OH)2 (CuPro and Kocide), micro Cu, micro CuO, ionic Cu(2+) (CuCl2 and CuSO4) in two species of bacteria (Escherichia coli and Lactobacillus brevis). The primary size of the particles studied ranged from 10 nm to 10 μm. Our results reveal that Cu and CuO nanoparticles (NPs) are more toxic than their microsized counterparts at the same Cu concentration, with toxicities approaching those of the ionic Cu species. Strikingly, these NPs showed distinct differences in their mode of toxicity when compared to the ionic and microsized Cu, highlighting the unique toxicity properties of materials at the nanoscale. In vitro DNA damage assays reveal that both nano Cu and microsized Cu are capable of causing complete degradation of plasmid DNA, but electron tomography results show that only nanoformulations of Cu are internalized as intact intracellular particles. These studies suggest that nano Cu at the concentration of 50 μg/mL may have unique genotoxicity in bacteria compared to ionic and microsized Cu.
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|§Molecular Toxicology Interdepartmental Degree Program, University of California, Los Angeles, California 90095, United States.|⊥Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, California 90095, United States.
authors.forename: Chitrada
authors.initials: C
authors.lastname: Kaweeteerawat
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Chang
authors.affiliation: ∥Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, California 90095, United States.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Roy
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|#Institute of the Environment and Sustainability, University of California, Los Angeles, California 90039, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Li
authors.affiliation: ∇Biomedical Engineering Interdepartmental Program, University of California, Los Angeles, California 90095, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Toso
authors.affiliation: ○Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California 90095, United States.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fischer
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|⊗Laboratory of Environmental Toxicology, National Institute of Chemical Physics and Biophysics, Tallinn, 12618, Estonia.
authors.forename: Angela
authors.initials: A
authors.lastname: Ivask
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Ji
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|◆Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Zink
authors.affiliation: ‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|×Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095, United States.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: ∥Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, California 90095, United States.
authors.forename: Guillaume Francois
authors.initials: GF
authors.lastname: Chanfreau
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|○Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles (UCLA), Los Angeles, California 90095, United States.
authors.forename: Donatello
authors.initials: D
authors.lastname: Telesca
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|#Institute of the Environment and Sustainability, University of California, Los Angeles, California 90039, United States.|◇Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, United States.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|+Bren School of Environmental Science and Management, University of California, and Earth Research Institute, Santa Barbara, California 93106, United States.
authors.forename: Patricia Ann
authors.initials: PA
authors.lastname: Holden
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|¶Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, United States.
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
authors.affiliation: †University of California Center for Environmental Implications of Nanotechnology, University of California, Los Angeles, California 90095, United States.|‡California NanoSystems Institute, University of California, Los Angeles, California 90095, United States.|§Molecular Toxicology Interdepartmental Degree Program, University of California, Los Angeles, California 90095, United States.|⊥Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, California 90095, United States.|#Institute of the Environment and Sustainability, University of California, Los Angeles, California 90039, United States.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Godwin
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000633:toxicity*; D003300:Copper / Q000737:chemistry / Q000633:toxicity*; D004926:Escherichia coli / Q000187:drug effects*; D052196:Levilactobacillus brevis / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D003300:Copper
keywords: antifouling; antimicrobial; copper; ecotoxity; genotoxicity; nanoparticle; nanotoxicology