Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis

PLoS Pathog. 2024 Jun 17;20(6):e1012319. doi: 10.1371/journal.ppat.1012319. eCollection 2024 Jun.

Abstract

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

MeSH terms

  • Biofilms* / growth & development
  • Candida albicans*
  • Candidiasis* / immunology
  • Candidiasis* / microbiology
  • Catheter-Related Infections* / microbiology
  • Catheters / microbiology
  • Extracellular Traps* / immunology
  • Fungal Proteins* / metabolism
  • Gene Expression Regulation, Fungal
  • Humans
  • Neutrophils* / immunology
  • Neutrophils* / metabolism

Substances

  • Fungal Proteins

Grants and funding

This work was supported by National Science and Technology Council, Taiwan (106-2321-B-010-015-MY3, 110-2320-B-A49A-544 -MY3, 111-2314-B-A49-046, 112-2314-B-A49-067) to YHT, and NYMU-FEMH Joint Research Program (109DN33) to YHT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.