Adherence of pathogens to extracellular matrix proteins and host cells is one of the essential steps in the microbial colonization of the human organism. The adhesion of C. glabrata, i.e. the second major causative agent of human disseminated candidiases after C. albicans, to the host epithelium mainly engages specific fungal cell wall proteins - epithelial adhesins (Epa) - in particular, Epa1, Epa6 and Epa7. The aim of the present study was to identify the major Epa protein involved in the interactions with the human extracellular matrix protein - fibronectin - and to present the kinetic and thermodynamic characteristics of these interactions. A relatively novel gel-free approach, i.e. the "cell surface shaving" that consists in short treatment of fungal cells with trypsin was employed to identify the C. glabrata surfaceome. Epa6 was purified, and the isolated protein was characterized in terms of its affinity to human fibronectin using a microplate ligand-binding assay and surface plasmon resonance measurements. The dissociation constants for the binding of Epa6 to fibronectin were determined to range between 9.03 × 10-9 M and 7.22 × 10-8 M, depending on the method used (surface plasmon resonance measurements versus the microplate ligand-binding assay, respectively). The identified fungal pathogen-human host protein-protein interactions might become a potential target for novel anticandidal therapeutic approaches.
Invasive fungal infection (IFI) in patients with malignant solid tumours is rare, but it highly increases the risk of cancer recurrence because of prolonged discontinuation of cancer treatment. This paper presents a case of IFI induced by Candida glabrata in a 14-year-old girl with advanced Ewing’s sarcoma and metastases to the bone marrow. She was intensively treated with chemotherapy (CWS, CEVAIE, EWING 2008 + VIDE) and radiotherapy. As the treatment was ineffective, the tumour was surgically removed from the sacrum, and VAI chemotherapy was administered. Due to the symptoms of infection, antifungal treatment was initiated with caspofungin, followed by prophylaxis with posaconazole. In terms of anti-cancer treatment, the patient received megatherapy with auto-HSCT. Signs of infection and gastrotoxic complications developed, which is why broad-spectrum antibiotics and amphotericin B lipid complex were administered. Even so, a multisystem IFI appeared, causing the patient’s death. In multidrug chemotherapy with extended periods of agranulocytosis, primary prevention should be considered, similar to the one offered to patients with haematological malignancies.
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