Project description:A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and T cell leukemia-derived cell line (Jurkat). TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify signaling pathways underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses, 1ug/ml and 10ug/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10ug/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that the gene expression of metallothioneins was upregulated in all the three cell types. In addition to the common ZnO-inducible changes, a notable proportion of the genes were regulated in a cell type-specific manner. Using a panel of ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is caused by particle dissolution. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Bioinformatics assessment showed that the top human disease category associated with ZnO-responsive genes in both HMDM and Jurkat cells was cancer. Overall, the study revealed novel genes and pathways for mediating ZnO nanoparticle-induced toxicity and demonstrated the value of assessing nanoparticle responses through combined transcriptomics and bioinformatics approach. Nanoparticles used in the study: ZnO-1 commercial (IBU-tec advanced materials AG), ZnO-2 (mandelic acid coated ZnO-1), ZnO-3 (mercaptopropyl-trimethoxysilane coated ZnO-1), ZnO-4 (methoxyl coated ZnO), ZnO-5 (diethylene glycol modified ZnO) and ZnO-9 (folic acid modified ZnO). Detailed particle production and characterization data can be found from the articles: Buerki-Thurnherr et al. 2012 Nanotoxicology and Tuomela et al.

Project description:An antivirulence approach targets bacterial virulence rather than cell viability in the antibiotic approach that can readily lead to drug resistance. Opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors, and biofilm cells of this bacterium are much more resistant to antibiotics than planktonic cells. To identify novel inorganic antivirulence compounds, the dual screenings of thirty-six metal ions were performed to identify that zinc ions and ZnO nanoparticle inhibited the pyocyanin production and biofilm formation in P. aeruginosa without affecting the growth of planktonic cells. Moreover, zinc ion and ZnO nanoparticle markedly reduced the production of 2-heptyl-3-hydroxy-4(1H)-quinolone and siderophore pyochelin, while increased the production of another sideropore pyoverdine and swarming motility. Further, zinc ion and ZnO nanoparticle clearly suppressed hemolytic activity in P. aeruginosa. Transcriptome analyses showed that ZnO nanoparticle induced zinc cation efflux pump czc operon, porin genes (oprD and opdT), and Pseudomonas type III repressor A ptrA, while repressed pyocyanin-related phz operon, which partially explains the phenotypic changes. Overall, ZnO nanoparticle is a potential candidate for use in an antivirulence approach against persistent P. aeruginosa infection. P. aeruginosa Genechip Genome Array (Affymetrix, P/N 900339) was used in order to study the cells after the addition of ZnO nanoparticles. DNA microarray analysis with one biological replicate was performed with an Affymetrix system. P. aeruginosa was inoculated in 25 ml of LB medium in 250 ml shaker flasks with overnight cultures (1 : 100 dilution). Cells were cultured for 5 h with shaking at 250 rpm with and without ZnO nanoparticles (1 mM). Before sample collection, RNase inhibitor (RNAlater, Ambion, TX, USA) was added, and the cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 s before centrifugation at 16,000 g for 2 min. The cell pellets were immediately frozen with dry ice and stored at –80°C. Total RNA was isolated using a Qiagen RNeasy mini Kit (Valencia, CA, USA).

Project description:A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and T cell leukemia-derived cell line (Jurkat). TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify signaling pathways underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses, 1ug/ml and 10ug/ml after 6 and 24 hours of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10ug/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that the gene expression of metallothioneins was upregulated in all the three cell types. In addition to the common ZnO-inducible changes, a notable proportion of the genes were regulated in a cell type-specific manner. Using a panel of ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is caused by particle dissolution. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Bioinformatics assessment showed that the top human disease category associated with ZnO-responsive genes in both HMDM and Jurkat cells was cancer. Overall, the study revealed novel genes and pathways for mediating ZnO nanoparticle-induced toxicity and demonstrated the value of assessing nanoparticle responses through combined transcriptomics and bioinformatics approach. Nanoparticles used in the study: ZnO-1 commercial (IBU-tec advanced materials AG), ZnO-2 (mandelic acid coated ZnO-1), ZnO-3 (mercaptopropyl-trimethoxysilane coated ZnO-1), ZnO-4 (methoxyl coated ZnO), ZnO-5 (diethylene glycol modified ZnO) and ZnO-9 (folic acid modified ZnO). Detailed particle production and characterization data can be found from the articles: Buerki-Thurnherr et al. 2012 Nanotoxicology and Tuomela et al. Altogether 71 samples were analyzed: 3 biological replicates of HMDM samples (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 biological replicates of MDDC samples (untreated control, 6 and 24 hours), 7 biological replicates of MDDC samples (10ug/ml of ZnO-1, 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-1, 6 and 24 hours), 3 replicates of Jurkat cells (untreated control, 10ug/ml of ZnO-2, ZnO-3, ZnO-5 or ZnO-9, or 10, 25, 50 or 100ug/ml of ZnO-4, 24 hours).

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Transcript abundance in C. necator grown with piezo-stimulated ZnO

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