Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candida albicans

Tim Kaden1, Raquel Alonso-Roman2, Parastoo Akbarimoghaddam3

  • 1Dynamic42 GmbH, Jena, Germany; Institute of Biochemistry II, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.

Biomaterials
|March 15, 2024
PubMed

Insights

A 3D intestine-on-chip model revealed how Candida albicans causes invasive candidiasis. This advanced model also evaluated antifungal drug efficacy against fungal-host interactions and microcolony development.

Area of Science:

  • Microbiology
  • Biomedical Engineering
  • Pathogen-Host Interactions

Background:

  • Candida albicans is a common gut microbe that can cause severe infections.
  • Traditional 2D cell models offer limited insight into complex fungal-host dynamics.
  • Advanced microphysiological systems are needed to better model in vivo infections.

Purpose of the Study:

  • To investigate fungal-host interactions during invasive candidiasis using a 3D intestine-on-chip model.
  • To evaluate the efficacy of antifungal treatment in a clinically relevant context.
  • To characterize fungal microcolony formation and tissue association.

Main Methods:

  • Utilized a 3D intestine-on-chip model to simulate human intestinal environment.
  • Employed microbiological and image-based analyses to quantify infection.
  • Assessed fungal invasiveness, translocation, and microcolony morphology.
  • Evaluated the impact of caspofungin treatment on wild-type and resistant strains.

Main Results:

  • C. albicans microcolonies induced epithelial injury, disrupted cell junctions, and triggered inflammation.
  • Caspofungin effectively reduced fungal load and altered microcolony morphology in wild-type infections.
  • Antifungal treatment showed limited efficacy against an echinocandin-resistant clinical isolate.
  • The model provided novel insights into fungal microcolony morphology and tissue association.

Conclusions:

  • The 3D intestine-on-chip model effectively mimics invasive candidiasis and antifungal treatment responses.
  • This model is valuable for studying pathogen-host interactions and antimicrobial efficacy.
  • Organ-on-chip technology offers a more biologically relevant platform for infection research.