Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria

Cell Host Microbe. 2022 Jul 13;30(7):1020-1033.e6. doi: 10.1016/j.chom.2022.04.013. Epub 2022 May 13.


Antibiotics are a modifiable iatrogenic risk factor for the most common human nosocomial fungal infection, invasive candidiasis, yet the underlying mechanisms remain elusive. We found that antibiotics enhanced the susceptibility to murine invasive candidiasis due to impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity within the gut. This led to non-inflammatory bacterial escape and systemic bacterial co-infection, which could be ameliorated by IL-17A or GM-CSF immunotherapy. Vancomycin alone similarly enhanced the susceptibility to invasive fungal infection and systemic bacterial co-infection. Mechanistically, vancomycin reduced the frequency of gut Th17 cells associated with impaired proliferation and RORγt expression. Vancomycin's effects on Th17 cells were indirect, manifesting only in vivo in the presence of dysbiosis. In humans, antibiotics were associated with an increased risk of invasive candidiasis and death after invasive candidiasis. Our work highlights the importance of antibiotic stewardship in protecting vulnerable patients from life-threatening infections and provides mechanistic insights into a controllable iatrogenic risk factor for invasive candidiasis.

Keywords: GM-CSF; IL-17A; antibiotics; invasive candidiasis; lymphocytes; trans-kingdom infections; vancomycin.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Bacteria / drug effects
  • Bacteria / immunology
  • Candida albicans / immunology
  • Candidiasis, Invasive* / immunology
  • Candidiasis, Invasive* / microbiology
  • Coinfection* / immunology
  • Coinfection* / microbiology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Iatrogenic Disease
  • Immunotherapy
  • Interleukin-17 / immunology
  • Interleukin-17 / therapeutic use
  • Mice
  • Th17 Cells / metabolism
  • Vancomycin / pharmacology


  • Anti-Bacterial Agents
  • Interleukin-17
  • Vancomycin
  • Granulocyte-Macrophage Colony-Stimulating Factor

Supplementary concepts

  • Systemic candidiasis