Abstract
BackgroundHospital acquired fungal infections are defined as “never events”—medical errors that should never have happened. Systemic Candida albicans infections results in 30–50% mortality rates. Typically, adhesion to abiotic medical devices and implants initiates such infections. Efficient adhesion initiates formation of aggressive biofilms that are difficult to treat. Therefore, inhibitors of adhesion are important for drug development and likely to have a broad spectrum efficacy against many fungal pathogens. In this study we further the development of a small molecule, Filastatin, capable of preventing C. albicans adhesion. We explored the potential of Filastatin as a pre-therapeutic coating of a diverse range of biomaterials.MethodsFilastatin was applied on various biomaterials, specifically bioactive glass (cochlear implants, subcutaneous drug delivery devices and prosthetics); silicone (catheters and other implanted devices) and dental resin (dentures and dental implants). Adhesion to biomaterials was evaluated by direct visualization of wild type C. albicans or a non-adherent mutant edt1−/− that were stained or fluorescently tagged. Strains grown overnight at 30 °C were harvested, allowed to attach to surfaces for 4 h and washed prior to visualization. The adhesion force of C. albicans cells attached to surfaces treated with Filastatin was measured using Atomic Force Microscopy. Effectiveness of Filastatin was also demonstrated under dynamic conditions using a flow cell bioreactor. The effect of Filastatin under microfluidic flow conditions was quantified using electrochemical impedance spectroscopy. Experiments were typically performed in triplicate.ResultsTreatment with Filastatin significantly inhibited the ability of C. albicans to adhere to bioactive glass (by 99.06%), silicone (by 77.27%), and dental resin (by 60.43%). Atomic force microcopy indicated that treatment with Filastatin decreased the adhesion force of C. albicans from 0.23 to 0.017 nN. Electrochemical Impedance Spectroscopy in a microfluidic device that mimic physiological flow conditions in vivo showed lower impedance for C. albicans when treated with Filastatin as compared to untreated control cells, suggesting decreased attachment. The anti-adhesive properties were maintained when Filastatin was included in the preparation of silicone materials.ConclusionWe demonstrate that Filastatin treated medical devices prevented adhesion of Candida, thereby reducing nosocomial infections.
Highlights
Hospital acquired fungal infections are defined as “never events”—medical errors that should never have happened
The double layer capacitance of the cell body and EPS results in Filastatin inhibits C. albicans adhesion in a time and concentration dependent manner We have previously demonstrated that Filastatin inhibits adhesion of many fungal pathogens of the Candida spp. to polystyrene surfaces [10]
Our results indicate that treatment with Filastatin significantly decreases adhesion by 58.7, 68.1 and 70.8%, respectively (p < 0.0001, one-way ANOVA) for C. albicans, as compared to the control (Fig. 1a)
Summary
Hospital acquired fungal infections are defined as “never events”—medical errors that should never have happened. The number of immunocompromised patients, the population “at risk” and susceptible to fungal diseases [5, 6], steadily increased worldwide at the beginning of the century due to better medical facilities and changes in life style As expected, this had serious repercussions in the number of reported cases of C. albicans infections [7, 8]. In the United States alone, the estimated healthcare cost to treat C. albicans systemic infections is between $1.5 and $2 billion per year, which accounts for ∼70% of the total amount spent on systemic fungal infections [9,10,11] This is in part due to a reduced number of antifungal drugs, a consequence of the fact that it is difficult to find fungi-specific drug targets that are not present on host cells. New methods to prevent hospital-acquired infections by this opportunistic fungus are becoming more important than ever
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