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Engineered Graphene Oxide Nanocomposite Capable of Preventing the Evolution of Antimicrobial Resistance

Huizhen ZhengState 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, ChinaZhaoxia JiDivision of Nanomedicine, Department of Medicine, California NanoSystems Institute, University of California, Los Angeles, California 90095, United StatesKevin RoyDepartment of Genetics, School of Medicine, Stanford University, Palo Alto, California 94304, United StatesMeng GaoState 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, ChinaYanxia PanState 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, ChinaXiaoming CaiSchool of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, ChinaLiming WangCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, 100049, ChinaWei LiState 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, ChinaChong Hyun ChangDivision of Nanomedicine, Department of Medicine, California NanoSystems Institute, University of California, Los Angeles, California 90095, United StatesChitrada KaweeteerawatNational Nanotechnology Center (NANOTEC), NSTDA Characterization and Testing Center (NCTC), National Science and Technology Development Agency (NSTDA), Klong Nueng, 12120, ThailandChunying ChenCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences (CAS), Beijing, 100190, ChinaTian XiaDivision of Nanomedicine, Department of Medicine, California NanoSystems Institute, University of California, Los Angeles, California 90095, United StatesYuliang ZhaoCAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences (CAS), Beijing, 100190, ChinaRuibin LiState 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
2019en
ABI

Abstract

Antimicrobial resistance (AMR) is spreading worldwide and keeps evolving to adapt to antibiotics, causing increasing threats in clinics, which necessitates the exploration of antimicrobial agents for not only killing of resistant cells but also prevention of AMR progression. However, so far, there has been no effective approach. Herein, we designed lanthanum hydroxide and graphene oxide nanocomposites (La@GO) to confer a synergistic bactericidal effect in all tested resistant strains. More importantly, long-term exposure of E. coli (AMR) to subminimum inhibitory concentrations of La@GO does not trigger detectable secondary resistance, while conventional antibiotics and silver nanoparticles lead to a 16- to 64-fold increase in tolerance. The inability of E. coli to evolve resistance to La@GO is likely due to a distinctive extracellular multitarget invasion killing mechanism involving lipid dephosphorylation, lipid peroxidation, and peptidoglycan disruption. Overall, our results highlight La@GO nanocomposites as a promising solution to combating resistant bacteria without inducing the evolution of AMR.

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