Biomimetic Nanosponges Enable the Detoxification of Vibrio vulnificus Hemolysin

Int J Mol Sci. 2022 Jun 19;23(12):6821. doi: 10.3390/ijms23126821.

Abstract

Vibrio vulnificus (V. vulnificus) infection-associated multiple antibiotic resistance has raised serious public health concerns. Recently, nanosponges (NSs) have been expected to provide innovative platforms for addressing antibacterial and drug-resistant challenges by targeting various pore-forming toxins (PFTs). In the present study, we constructed NSs to explore the effects and possible mechanism of recombinant V. vulnificus hemolysin (rVvhA)-induced injuries. In vitro, NSs significantly reversed rVvhA-induced apoptosis and necrosis, and improved toxin-induced intracellular reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, and apoptosis signaling pathway disruption. To explore the clinical translation potential of NSs, we established VvhA-induced septicemia and wound infection mouse models, respectively, and further found NSs could notably attenuate rVvhA-induced acute toxicity and septicemia-associated inflammation, as well as local tissue damage. In a conclusion, NSs showed excellent protective effects against rVvhA-induced toxicity, thus providing useful insights into addressing the rising threats of severe V. vulnificus infections.

Keywords: Vibrio vulnificus; VvhA; biodetoxification; nanosponge; pore-forming toxins.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biomimetics
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Mice
  • Reactive Oxygen Species / metabolism
  • Sepsis*
  • Vibrio Infections*
  • Vibrio vulnificus*

Substances

  • Bacterial Proteins
  • Hemolysin Proteins
  • Reactive Oxygen Species