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Genome Wide Assessment in Escherichia coli Reveals Time Dependent Nanotoxicity Paradigms.
MedLine Citation:
PMID:  23039911     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The use of engineered nanomaterials (eNM) in consumer and industrial products is increasing exponentially. Our ability to rapidly assess their potential effects on human and environment health is limited by our understanding of nano-mediated toxicity. The use of high throughput experimentation enables probeing the nano-mediated toxicity on a genome wide level, thus uncovering their novel mechanisms and paradigms. Herein, we investigate the toxicity of zinc containing nanomaterials (Zn-eNMs) using a time-resolved high throughput screening (HTS) methodology in an arrayed Escherichia coli genome-wide knockout library. The library was screened against nanoscale zero-valent zinc (nZn), nanoscale zinc oxide (nZnO), and zinc chloride (ZnCl2) salt for reference. Through sequential screening over 24 hours, our method identified 173 sensitive clones from diverse biological pathways, which fell into two general groups: early and late responders. The overlap between these groups was small. Our results suggest bacterial toxicity mechanisms vary with time, and change from pathways related to general metabolic function, transport, signaling, and metal ion homeostasis during earlier time points to membrane synthesis pathways at later time points. Furthermore, we found differences in the sensitivity profiles between Zn-eNMs and respective Zn-salt with overlapping pathways related to membrane damage and metal ion homeostasis. Uniquely, ZnCl2 elicited responses in pathways related to two-component signaling, while e.g. nZnO evoked responses in pathways related to monosaccharide biosynthesis. In conclusion, single isolated measurements, such as MIC or IC50 are inadequate and time resolved approaches utilizing genome wide assays are needed to capture this crucial dimension and illuminate the dynamic interplay at the nano-bio interface.
Authors:
Vince Reyes; Minghua Li; Eric M V Hoek; Shaily Mahendra; Robert Damoiseaux
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-6
Journal Detail:
Title:  ACS nano     Volume:  -     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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