Fungal Cell Wall: Emerging Antifungals and Drug Resistance.
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TLDR
This review summarizes recent findings regarding antifungal therapy and development of resistance related to the fungal cell wall of the most relevant human pathogenic species.Abstract:
The cell wall is an essential component in fungal homeostasis. The lack of a covering wall in human cells makes this component an attractive target for antifungal development. The host environment and antifungal stress can lead to cell wall modifications related to drug resistance. Antifungals targeting the cell wall including the new β-D-glucan synthase inhibitor ibrexafungerp and glycosyl-phosphatidyl Inositol (GPI) anchor pathway inhibitor fosmanogepix are promising weapons against antifungal resistance. The fosmanogepix shows strong in vitro activity against the multidrug-resistant species Candida auris, Fusarium solani, and Lomentospora prolificans. The alternative carbon sources in the infection site change the cell wall β-D-glucan and chitin composition, leading to echinocandin and amphotericin resistance. Candida populations that survive echinocandin exposure develop tolerance and show high chitin content in the cell wall, while fungal species such as Aspergillus flavus with a higher β-D-glucan content may show amphotericin resistance. Therefore understanding fungal cell dynamics has become important not only for host-fungal interactions, but also treatment of fungal infections. This review summarizes recent findings regarding antifungal therapy and development of resistance related to the fungal cell wall of the most relevant human pathogenic species.read more
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APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia.
Suganya Viriyakosol,Mili Kapoor,Sharon Okamoto,Jonathan Covel,Quinlyn A. Soltow,Michael Trzoss,Karen Joy Shaw,Joshua Fierer +7 more
TL;DR: ABSTRACT APX001A is the first in a new class of broad-spectrum antifungal agents that inhibit Gwt1, an enzyme which is required for cell wall localization of glycosylphosphatidylinositol (GPI)-anchored mannoproteins in fungi and may offer great promise as effective therapies for coccidioidomycosis.
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Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall.
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TL;DR: A comprehensive review of the progress made to date in the development of fungal cell wall inhibitors is provided, focusing on the targets, discovery process, chemical structures, antifungal activities and structure-activity relationships.
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Advances in Biomaterials for the Prevention and Disruption of Candida Biofilms.
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Camphor and Eucalyptol-Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity.
Marija Ivanov,Abhilash Kannan,Dejan Stojković,Jasmina Glamočlija,Ricardo C. Calhelha,Isabel C.F.R. Ferreira,Dominique Sanglard,Marina Soković +7 more
TL;DR: Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have been explored previously as mentioned in this paper, which showed that Camphor's potential to reduce fungal virulence traits, that is, biofilm establishment and hyphae formation.
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