Abstract

Traditional in vivo investigation of fungal infection and new antifungal therapies in mouse models is usually carried out using post mortem methodologies. However, biomedical imaging techniques focusing on non-invasive techniques using bioluminescent and fluorescent proteins have become valuable tools. These new techniques address ethical concerns as they allow reduction in the number of animals required to evaluate new antifungal therapies. They also allow better understanding of the growth and spread of the pathogen during infection. In this review, we concentrate on imaging technologies using different fungal reporter proteins. We discuss the advantages and limitations of these different reporters and compare the efficacy of bioluminescent and fluorescent proteins for fungal research.

Highlights

  • Traditional in vivo investigation of fungal infection and new antifungal therapies in mouse models is usually carried out using post mortem methodologies

  • As eukaryotic pathogens causing a range of infections, pathogenic fungi present specific challenges to human health and it is essential that we develop a better understanding of their pathogenicity and interactions with the host

  • Current antifungals to treat fungal infections are limited to four classes: polyenes, azoles, echinocandins and 5-fluorocytosine (5-FC) [4,5], with amphotericin B, fluconazole and 5-FC featuring on the WHO Essential Medicine List [6]

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Summary

Fungi and Infection

Infections by fungi, e.g., Candida, Aspergillus and Cryptococcus species, are increasing threats to human health [1]. Current antifungals to treat fungal infections are limited to four classes: polyenes, azoles, echinocandins and 5-fluorocytosine (5-FC) [4,5], with amphotericin B (a polyene), fluconazole (an azole) and 5-FC featuring on the WHO Essential Medicine List [6] These drugs are not fully effective in severe infections and are toxic to the patient [7,8]. The availability of amphotericin B and 5-FC in certain countries in Africa with high burdens of fungal infection and the local high cost of other antifungals, such as fluconazole, is a global health issue [9,10] Another issue in antifungal treatment is the difference in efficacy of a drug in different fungal infections; e.g., echinocandin drugs, such as caspofungin or micafungin, are effective against candidiasis [11,12]; they have no impact on Cryptococcus infections [13]. Cryptic infection sites may be missed when these models are used [27]

Novel Non-Invasive Techniques
Key Challenges of In Vivo Imaging of Fungal Infections
Bioluminescent Imaging
Fluorescent Imaging and iRFP
Near-Infrared Fluorescent Protein
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