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In vivo imaging of the activity of host defense peptide mimetics in a mouse model of invasive candidiasis
Gill Diamond * 1 , Lisa K Ryan 1 , Rezwana Parveen 1 , Amy Hise 2 , Katie B Freeman 3 , Richard W Scott 3
1  University of Florida
2  Case Western Reserve University
3  Fox Chase Chemical Diversity Center

Published: 03 November 2018 by MDPI AG in 4th International Electronic Conference on Medicinal Chemistry session ECMC-4
10.3390/ecmc-4-05628
Abstract:

Systemic fungal infections are increasingly common, especially in immune compromised patients. Even with newly developed drugs, there remain issues of limited spectrum, side effects, and the development of resistance. Host defense peptides (HDPs) have been examined recently for their utility as therapeutic antifungals, especially due to the low levels of resistance that develop. Unfortunately, the peptides exhibit poor pharmacologic properties in vivo. We have demonstrated the potent activity of nonpeptidic compounds that mimic HDPs in both structure and function against clinical strains of Candida albicans associated with oral and invasive candidiasis in mouse models. However, to test numerous compounds in vivo requires large numbers of mice, with multiple time points, and requires immunosuppression of the mice using cyclophosphamide, which can influence pharmacological parameters. We have identified a strain of mouse that develops invasive candidiasis without the need for immunosuppressive drugs. When we infect these mice with a strain of C. albicans that constitutively expresses Red Fluorescent Protein, we can quantify the infection in real time by in vivo imaging. We can further observe the reduction in fluorescence in infected mice after treatment with an HDP mimetic. Together our results demonstrate a novel in vivo method for screening new antifungal drugs.

Keywords: antimicrobial peptide, antifungal, Candida, peptidomimetics
Comments on this paper
Bethany Roberts
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I'm not sure that many are familiar with this work from the University of Florida. But I can say that as a professional specialist in this field I was very pleased to read this work. I understood many things that I wrote in college. We were often asked to write essays. If I didn’t work well, I found the information useful reference. I did the same when I wrote not only an essay but also my dissertation.



 
 
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