Frontiers in Microbiology (May 2019)

Vancomycin-Loaded Nanoparticles Enhance Sporicidal and Antibacterial Efficacy for Clostridium difficile Infection

  • Yi-Hsuan Chen,
  • Yi-Hsuan Chen,
  • Tsung-Ju Li,
  • Bo-Yang Tsai,
  • Liang-Kuei Chen,
  • Yi-Hsin Lai,
  • Meng-Jia Li,
  • Cheng-Yang Tsai,
  • Pei-Jane Tsai,
  • Pei-Jane Tsai,
  • Pei-Jane Tsai,
  • Dar-Bin Shieh,
  • Dar-Bin Shieh,
  • Dar-Bin Shieh,
  • Dar-Bin Shieh

DOI
https://doi.org/10.3389/fmicb.2019.01141
Journal volume & issue
Vol. 10

Abstract

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Current antibiotic treatments fail to eliminate the Clostridium difficile (C. difficile) spores and induce dysbiosis and intestinal inflammation via off-target effect, which causes refractory C. difficile infection raise an unmet need for a spore-specific antimicrobial treatment. We developed a sporicidal and antimicrobial vancomycin-loaded spore-targeting iron oxide nanoparticle (van-IONP) that selectively binds to C. difficile spores. Cryo-electron microscopy showed that vancomycin-loaded nanoparticles can target and completely cover spore surfaces. They not only successfully delayed the germination of the spores but also inhibited ∼50% of vegetative cell outgrowth after 48 h of incubation. The van-IONPs also inhibited the interaction of spores with HT-29 intestinal mucosal cells in vitro. In a murine model of C. difficile infection, the van-IONP significantly protected the mice from infected by C. difficile infection, reducing intestinal inflammation, and facilitated superior mucosal viability compared with equal doses of free vancomycin. This dual-function targeted delivery therapy showed advantages over traditional therapeutics in treating C. difficile infection.

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