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

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.

Nanosilver Mitigates Biofilm Formation via FapC Amyloidosis Inhibition

“…In another study, silver bromide nanoparticle‐pyridinium polymeric composites adhered onto glass substrates and exhibited long‐term biocidal properties against airborne and waterborne bacteria . Furthermore, lanthanum hydroxide–graphene oxide nanocomposites (La@GO) conferred strong bactericidal effects on both wild‐type and antibiotic‐resistant E. coli , Lactobacillus crispatus , Staphylococcus aureus , and P. aeruginosa strains …”

Molecular Mechanisms, Characterization Methods, and Utilities of Nanoparticle Biotransformation in Nanosafety Assessments

“…While Fang et al identified substantial Pd NPs in Escherichia coli cells by energy dispersive spectroscopy (EDS) mapping, [56] graphene oxides were found to mainly associate with cell membranes. [72] For AgNPs, they were found to accumulate at the outer membrane and also in the periplasm, plasma membrane and cytoplasm of E. coli. [73] However, it is hard to rule out the possibility that precipitation of Ag ions in cytoplasm to form nanosized structures.…”

“…After the depletion of free phosphates, the lanthanide ions may grab phosphates from phospholipids or proteins and induce lysosomal permeabilization or plasma membrane damages. [72] The recrystallization includes three stages: whisker, whisker growth, and maturation of urchin-shaped structures. This recrystallization process at physiological conditions was determined by the solubility of rare earth NPs in acidic lysosomes and precipitation of lanthanide phosphates (Figure 4).…”

“…[188] In our recent study, 3D nanocomputed tomography (nano-CT) via synchrotron radiation was explored to visualize the biotransformation of graphene oxide-lanthanum composites in bacteria membranes. [72] Figure 5. Confocal microscopy imaging of fluorophore labeled NPs: GO and Gd 2 O 3 were labeled by FITC or FITC-tagged proteins to incubate with mammalian cells and observed the particle distribution.…”

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

“…Graphene oxide (GO) nanoparticles (NPs) have been widely used in biomedical fields due to their physical and chemical properties, which make them useful for applications in as drug delivery [1,2], tumor photothermal therapy [3][4][5], bioimaging [6], tissue engineering [7,8], antimicrobial agents [9,10], biosensors [11][12][13][14]. At the same time, the risk of human contact has increased dramatically.…”