Chronic Exposure to Low Concentration of Graphene Oxide Increases Bacterial Pathogenicity via the Envelope Stress Response

Abstract

Graphene oxide (GO), which has diverse antimicrobial mechanisms, is a promising material to address antibiotic resistance. Considering the emergence of antibiotic tolerance/resistance due to prolonged exposure to sublethal antibiotics, it is imperative to assess the microbiological effects and related adaptive mechanisms under chronic exposure to sublethal levels of GO, which have rarely been explored. After repetitive exposure to 5 mg/L GO for 200 subcultures (400 days), evolved Escherichia coli (E. coli) cells (E GO) differed significantly from their ancestor cells according to transcriptomic and metabolomic analyses. Contact with GO surfaces transformed E. coli by activating the Cpx envelope stress response (ESR), resulting in more than twofold greater extracellular protease release and biofilm formation. The ESR also modulated the envelope structure and function via increases in membrane fluidity, permeation, and lipopolysaccharide content to fulfill growth requirements and combat envelope stress. As a consequence of metabolic adjustment, E GO cells showed advantages of surviving in an acidic and oxidative environment, which resembles the cytosol of host cells. With these adaptive features, E GO cells exhibited higher pathogenicity than ancestor E. coli cells as evidenced by increased bacterial invasion and intracellular survival and a more severe inflammatory response in macrophage cells. To conclude, we seek to raise awareness of the possible occurrence of microbial adaptation to antimicrobial nanomaterials, which may be implicated in cross-adaptation to harsh environments and eventually the prevalence of virulence.

Uptake Route Altered the Bioavailability of Graphene in Misgurnus anguillicaudatus: Comparing Waterborne and Sediment Exposures

“…One loach was added to a 500 mL jar containing a 250 mL 14 C-FLG suspension (50 μg/L and 250 μg/L). Notably, the concentrations of 14 C-FLG were selected based on a predicted environmental concentration of carbon nanotubes (approximately 1–1000 μg/L), − because these two materials possess a number of similarities (e.g., application fields and release characteristics) and may have a similar fate. , A jar containing only freshwater was used as the control. (2) Sediment exposure: 250 mL of a 14 C-FLG suspension was slowly added into a 500 mL jar containing sediments with a depth of 4 cm, which was left to settle for 4 h, and the supernatant became clear.…”

Addressing a future pandemic: how can non-biological complex drugs prepare us for antimicrobial resistance threats?

“…117 Very recently, Zhang et al demonstrated that E. coli exposed to sublethal concentrations of graphene oxide over 200 passages resulted in significant alterations to both the transcriptome and the metabolic behavior through activation of an induced envelope stress response. 118 These adaptations allowed improved survival in harsh oxidative and low pH environments and facilitated greater pathogenicity through increased biofilm formation and extracellular protease release, greater bacterial invasion and intracellular survival, and greater macrophage inflammatory response. 117 This study highlights the unforeseen impact of low levels of such nanomaterials in the environment, with serious implications for human and animal health.…”

Nanomaterial Shape Influence on Cell Behavior

“…Li et al [ 198 ] found that spherical and nanosheet carbon nanomaterials positively affect the upregulation of genes involved in amino acid and carbohydrate metabolism. Zhang et al studied the effect of chronic exposure to low concentrations of graphene oxide on Escherichia coli [ 199 ]. The interaction between graphene oxide and bacteria causes the significant activation of the Cpx envelope stress response, resulting in a more than two-fold increase of extracellular protease release and biofilm formation.…”