Huizhen Zheng1, Zonglin Gu2, Yanxia Pan1, Jie Chen1, Qianqian Xie1, Shujuan Xu1, Meng Gao1, Xiaoming Cai3, Shengtang Liu1, Weili Wang1, Wei Li1, Xi Liu1, Zaixing Yang4, Ruhong Zhou1,5, Ruibin Li6. 1. State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, Jiangsu, China. 2. Institute of Quantitative Biology, Department of Physics, Zhejiang University, Hangzhou, 310027, Zhejiang, China. 3. School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, China. 4. State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, Jiangsu, China. zxyang@suda.edu.cn. 5. Department of Chemistry, Columbia University, New York, NY, 10027, USA. 6. State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, Jiangsu, China. liruibin@suda.edu.cn.
Abstract
BACKGROUND: Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. RESULTS: This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G-) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G- and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G- cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G-/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G-/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. CONCLUSIONS: This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G- and G+ bacteria and disclosed that La2O3-induced membrane damages of G- cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.
BACKGROUND: Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. RESULTS: This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G-) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G- and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G- cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G-/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G-/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. CONCLUSIONS: This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G- and G+ bacteria and disclosed that La2O3-induced membrane damages of G- cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.
Authors: Alexander P Richter; Joseph S Brown; Bhuvnesh Bharti; Amy Wang; Sumit Gangwal; Keith Houck; Elaine A Cohen Hubal; Vesselin N Paunov; Simeon D Stoyanov; Orlin D Velev Journal: Nat Nanotechnol Date: 2015-07-13 Impact factor: 39.213
Authors: Filipe Natalio; Rute André; Aloysius F Hartog; Brigitte Stoll; Klaus Peter Jochum; Ron Wever; Wolfgang Tremel Journal: Nat Nanotechnol Date: 2012-07-01 Impact factor: 39.213
Authors: Florence Mus; Matthew B Crook; Kevin Garcia; Amaya Garcia Costas; Barney A Geddes; Evangelia D Kouri; Ponraj Paramasivan; Min-Hyung Ryu; Giles E D Oldroyd; Philip S Poole; Michael K Udvardi; Christopher A Voigt; Jean-Michel Ané; John W Peters Journal: Appl Environ Microbiol Date: 2016-06-13 Impact factor: 4.792
Authors: Limin Zhang; Robert G Nichols; Jared Correll; Iain A Murray; Naoki Tanaka; Philip B Smith; Troy D Hubbard; Aswathy Sebastian; Istvan Albert; Emmanuel Hatzakis; Frank J Gonzalez; Gary H Perdew; Andrew D Patterson Journal: Environ Health Perspect Date: 2015-03-13 Impact factor: 9.031