Device to measure fungal biofilm dispersion

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Project Overview

As medical technology has advanced, the use of a variety of medical devices has proliferated. Unfortunately, many of the invasive life-sustaining devices necessary for delicate patient populations disrupt the patientís natural protective barriers (e.g. skin, mucosal membranes) and provide a natural conduit for infection. At least half of all hospital-acquired infections are associated with a medical device. Invasive fungal infections in particular represent a devastating complication associated with high mortality and high morbidity. Candida yeast species cause 80-90% of these infections and it is estimated that anywhere from 15-50% of patients who develop invasive Candida infections die.

Medical devices are colonized by fungal biofilms when planktonic cells adhere to the device and develop into highly structured communities comprised of layers of yeast, pseudohyphae, and hyphae embedded in an extracellular matrix. These biofilms serve as reservoirs of infection; yeast-form cells dispersed from the biofilm seed metastatic infections and are the main culprits associated with establishment of invasive disease. Experimental and clinical evidence suggests that Candida biofilms incapable of dispersion are relatively avirulent. Thus, it appears it is the release of cells from the device-associated biofilm that leads to fatal infection and not establishment of the biofilm per se. This suggests that inhibition of dispersion would be a viable antifungal strategy for preventing the mortality and morbidity associated with fungal biofilms. However to date the majority of research and development has been focused on understanding, preventing, and disrupting formation of biofilms. An experimental device for measuring dispersion is desperately needed to advance our understanding of the cues that cause cells to disperse from fungal biofilms and how this process might be prevented.

The goal of this project is to design a device for experimentally measuring dispersion from fungal biofilms. This device should allow a fungal biofilm to be established within the device and cells dispersed from the biofilm to be collected for quantification and assessment of virulence properties such as adhesion and invasiveness. The device should allow the biofilm to be exposed to different environmental conditions, such as nutrient depletion or antifungal drugs, so that the effect of the environment on biofilm dispersion can be tested. The device should be amenable to miniaturization and parallelization so that many biofilms can be tested at the same time allowing us to assess dispersion in different mutant strains and under different conditions in a medium-throughput manner. Finally, the ability to monitor biofilm development and dispersion using light-microscopy throughout the course of the experiment would be ideal.

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Team members from left to right: Madalyn, Becca, Nick, Jason

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