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Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2014 Jul; Vol. 58 (7), pp. 3820-7. Date of Electronic Publication: 2014 Apr 21. - Publication Year :
- 2014
-
Abstract
- There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.<br /> (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- 3T3 Cells
Animals
Anti-Bacterial Agents pharmacology
Antifungal Agents chemistry
Bacteria drug effects
Cell Survival
Drug Resistance, Fungal
High-Throughput Screening Assays
Hyphae chemistry
Immunocompromised Host
Male
Mice
Microbial Sensitivity Tests
Molecular Mimicry
Peptides chemistry
beta-Defensins pharmacology
Antifungal Agents pharmacology
Candida albicans chemistry
Candidiasis, Oral microbiology
Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 58
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 24752272
- Full Text :
- https://doi.org/10.1128/AAC.02649-13