We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.
- Authors
Tseng, Kuo-Yao; Huang, Yu-Tsung; Huang, Yu-Ting; Su, Yu-Ting; Wang, An-Ni; Weng, Wen-Yen; Ke, Cai-Ling; Yeh, Yu-Chiao; Wang, Jhih-Jie; Du, Shin-Hei; Gu, Zi-Qi; Chen, Wei-Lin; Lin, Ching-Hsuan; Tsai, Yu-Huan
- 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. Author summary: Intravascular catheters are widely used to administer medication and provide nutritional support to patients. However, their clinical use also increases the incidence of bloodstream infections and constitutes a risk factor for Candida albicans infection. Microbial biofilms have been proposed as the primary living style of microbes on a surface, including those on intravascular catheters. Numerous studies focus on identifying microbial factors contributing to C. albicans biofilm formation. However, our understanding of the host factors involved in controlling C. albicans biofilms on the surface of intravascular catheters is limited. In this study, we demonstrated that the biofilms in intravascular catheters removed from candidiasis patients comprised not only C. albicans cells but also human immune cells. Among these catheters, the immune cells interacting with the fungus exhibited different properties of NETosis, a type of neutrophil cell death with antimicrobial activity. We further showed that the catheter isolates exhibited reduced expression of candidalysin. Supplementation of candidalysin promoted NETosis induced by C. albicans biofilms and diminished C. albicans biofilms on a surface. Our findings highlight the implication of neutrophils in eliminating C. albicans biofilms, and point out the benefit of reduced candidalysin expression for C. albicans to persist in intravascular catheters.
- Subjects
CANDIDA albicans; CATHETERS; CATHETER-related infections; CANDIDIASIS; GENE expression; PARENTERAL feeding
- Publication
PLoS Pathogens, 2024, Vol 20, Issue 6, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1012319