A synthetic peptide mimic kills Candida albicans and synergistically prevents infection
This article has been Reviewed by the following groups
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomical, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited. Here we investigate the antifungal mode of action and therapeutic potential of positively charged, synthetic peptide mimics to combat infections by Candida albicans . These synthetic polymers cause stress to the endoplasmic reticulum and affect protein glycosylation, a distinct mode of action compared to currently approved antifungal drugs. The most promising polymer composition caused damage to the mannan layer of the cell wall, with additional membrane-disrupting activity. The synergistic combination of the polymer with caspofungin prevented infection of human epithelial cells in vitro , improved fungal clearance by human macrophages, and significantly increased host survival in a Galleria mellonella model of systemic candidiasis. Additionally, prolonged exposure of C. albicans to the synergistic combination of polymer and caspofungin did not lead to the evolution of resistant strains in vitro . Together, this work highlights the enormous potential of these synthetic peptide mimics to be used as novel antifungal formulations as well as adjunctive antifungal therapy.
Article activity feed
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Laxmi Rai
Review 2: "A Synthetic Peptide Mimic Kills Candida Albicans and Synergistically Prevents Infection"
Reviewers provided positive feedback on the rationale, methods, and findings. The reviewers recognized the novelty of using these mimics as anti-fungal agents alone or in combination therapy.
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Hong Xin
Review 1: "A Synthetic Peptide Mimic Kills Candida Albicans and Synergistically Prevents Infection"
Reviewers provided positive feedback on the rationale, methods, and findings. The reviewers recognized the novelty of using these mimics as anti-fungal agents alone or in combination therapy.
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Strength of evidence
Reviewers: H Xin (Louisiana State University) | 📗📗📗📗◻️
L Rai (GITAM University) | 📗📗📗📗◻️ -