Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy

ACS Nano. 2022 Sep 27;16(9):14860-14873. doi: 10.1021/acsnano.2c05756. Epub 2022 Sep 12.

Abstract

Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.

Keywords: antibacterial; bismuth sulfide; multi-drug-resistant bacteria; peritonitis; phototherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Antioxidants
  • Bacteria / metabolism
  • Bacterial Infections* / drug therapy
  • Bismuth
  • CD8-Positive T-Lymphocytes
  • Glucose
  • Humans
  • Immunotherapy
  • Nanoparticles* / chemistry
  • Peroxynitrous Acid
  • Phototherapy
  • RNA
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins
  • S-Nitrosothiols*
  • Sulfides / chemistry
  • Sulfides / pharmacology
  • Sulfides / therapeutic use
  • Tetracyclines

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Reactive Oxygen Species
  • Recombinant Proteins
  • S-Nitrosothiols
  • Sulfides
  • Tetracyclines
  • Peroxynitrous Acid
  • RNA
  • Glucose
  • Acetylcholine
  • Bismuth
  • bismuth sulfide