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Biomaterial-associated infection with Candida albicans in mice
B Rózalska1, A Ljungh, A Burow
1Department of Infectious Biology, University of Lódź, Poland.
Abstract:
Candida yeasts are frequently isolated from patients with continuous ambulatory peritoneal dialysis peritonitis or other biomaterial-associated infections. The mouse model of candidal peritonitis was used to study the interaction of Candida cells with end-point attached heparinized polyethylene (H-PE) and with polymorphonuclear leukocytes (PMNs) or macrophages (M phi). Two Candida strains differing in cell surface hydrophobicity and in expression of fibronectin (Fn) binding were used for the study. Cells of both Candida strains adhered at higher numbers to H-PE surfaces preadsorbed with Fn or with human dialysis fluid (HDF) than to non-modified H-PE, supporting a role of Fn in mediating adhesion. C. albicans 4016 cells expressing low hydrophobicity and low binding of soluble Fn demonstrated stronger adhesion to PMNs than the more hydrophobic C. albicans 3248 yeasts, which express high binding of soluble Fn. However, C. albicans 4016 cells were more resistant to phagocytic killing and were hardly eradicated in intraperitoneally infected mice. The animals depleted in PMNs by treatment with CY were neither able to eradicate C. albicans 3248 (rapidly eliminated by normal mice) nor C. albicans 4016 yeasts (with a tendency to persist in the tissues of normal mice).
Insights
Candida yeasts adhere to medical devices, with fibronectin enhancing this interaction. Strain properties influence immune cell interaction and infection outcomes in a mouse model, highlighting the complexity of biomaterial-associated infections.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Biomaterials Science
Background:
- Candida yeasts are common causes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).
- Biomaterial-associated infections, particularly those involving medical devices like catheters, are a significant clinical challenge.
- Understanding Candida's interaction with host cells and biomaterials is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the adherence of Candida yeasts to heparinized polyethylene (H-PE) biomaterials.
- To examine the interaction between different Candida strains and host immune cells (polymorphonuclear leukocytes and macrophages).
- To evaluate the role of cell surface properties, such as hydrophobicity and fibronectin binding, in Candida infections.
Main Methods:
- Utilized a mouse model of candidal peritonitis.
- Assessed Candida yeast adhesion to H-PE surfaces modified with fibronectin (Fn) and human dialysis fluid (HDF).
- Studied the interaction of two distinct Candida strains with polymorphonuclear leukocytes (PMNs) and macrophages (M phi).
- Evaluated fungal clearance and persistence in infected mice, including experiments with PMN-depleted animals.
Main Results:
- Candida strains showed increased adherence to Fn- and HDF-coated H-PE surfaces compared to unmodified H-PE, indicating fibronectin's role in mediating adhesion.
- A less hydrophobic Candida strain (C. albicans 4016) with low fibronectin binding exhibited stronger adhesion to PMNs than a more hydrophobic strain (C. albicans 3248) with high fibronectin binding.
- C. albicans 4016 was more resistant to phagocytic killing and persisted in infected mice, while C. albicans 3248 was rapidly cleared in normal mice.
- PMN depletion significantly impaired the clearance of both Candida strains, underscoring the critical role of PMNs in controlling candidal peritonitis.
Conclusions:
- Fibronectin plays a significant role in mediating Candida yeast adhesion to biomaterials used in medical devices.
- Candida strain characteristics, including hydrophobicity and fibronectin binding, influence interactions with immune cells and subsequent infection dynamics.
- Polymorphonuclear leukocytes are essential for controlling Candida peritonitis, and their depletion leads to persistent infections, irrespective of fungal strain properties.