Reducing animal usage in antifungal drug development: iRFP reporter strains and imaging infection

Fungal infections are a continuing problem globally. Mortality rates remain high, partially due to limited therapeutic options and increasing resistance to currently available antifungal agents. This has driven a need to identify and evaluate new antifungals. Currently, a major step in the pre-clinical development of new antifungals is the evaluation of their efficacy in mouse infection models. In most cases this relies upon survival curves and sampling groups of mice at different times to evaluate the antifungal effects on fungal burdens.

We have previously developed a near infrared (iRFP) reporter strain of Candida albicans in an NC3Rs funded pilot project which we have demonstrated can be imaged in infected animals. In this project we will further evaluate this reporter strain in response to antifungal agents and aim to reduce the number of animals required to evaluate a new antifungal agent by 36%. We will also develop iRFP reporter strains for Aspergillus fumigatus and Cryptococcus neoformans, allowing live imaging of these infections and responses to antifungal therapy. Excitingly, our industrial collaborators have indicated their support for this project and will supply us with novel antifungal agents in the later phase of the studentship, allowing the PhD student to demonstrate the utility of this model for antifungal drug development.

• Further Funding: NC3Rs Pilot Study Grant, Live real-time imaging of life-threatening invasive fungal infections, July 2013, £76,139 
• Further Funding: NC3Rs PhD Studentship, An in vitro model system to assay kidney-pathogen interactions determining outcome of Candida albicans infection, October 2010, £120,000