Characterisation of the anticryptococcal effect of the FC‐1 toxin produced by Filobasidium capsuligenum

Abstract

The basidiomycetous yeast Filobasidium capsuligenum produces a killer toxin (FC-1) which is highly effective against the opportunistic fungal pathogen Cryptococcus neoformans. The aim of this work was to study the effect of the toxin on C. neoformans cells. The sensitivities of strains representing eight molecular subtypes (VNI-IV and VGI-IV) of the C. neoformans species complex, and of an additional 50 clinical and environmental isolates were determined. Analysis of cellular DNA by laser scanning cytometry and fluorescein isothiocyanate (FITC) staining of the toxin-treated cells revealed that the killing mechanism of FC-1 is neither cell cycle- nor cell wall biosynthesis-dependent; rather it may act as an ionophoric protein that disrupts the cytoplasmic membrane function. The competition assay results suggest that beta-1,6-glucan in the cell wall may provide the binding site for the killer protein. This anticryptococcal toxin has the potential to be applied as a therapeutic agent for the treatment of cryptococcosis.

From yeast killer toxins to antibiobodies and beyond

“…Double‐stranded mycoviral RNA‐encoded KTs in Saccharomyces cerevisiae bind to β‐1,6‐glucan (K1 and K2) or α‐1,3‐linked mannose residues in the mannoprotein layer (K28). Other KTs can interact with β‐1,6‐glucan, such as Pichia membranifaciens (PM)KT and FC‐1 from Pichia membranifaciens (Santos et al , 2007) and Filobasidium capsuligenum (Keszthelyi et al , 2006), respectively. Zygocin from Zygosaccharomyces bailii (Weiler & Schmitt, 2003) binds to an α‐1,3‐mannoprotein, while chitin acts as a primary KTR of different heteromeric KTs from Kluyveromyces lactis (zymocin), Pichia acaciae, Pichia inositovora and Wingea robertsiae , among others (Jablonowski & Schaffrath, 2007).…”

Susceptibility of species within the Sporothrix schenckii complex to a panel of killer yeasts

“…S. cerevisiae K1 and K2 toxins exhibit their lethal effect on sensitive cells by disrupting the cytoplasmic membrane function [10]; the K28 toxin has no ionophoric effect, but it inhibits both nuclear DNA synthesis and the budding cycle [30]. Filobasidium capsuligenum FC-1 toxin releases cellular components through pores formed in the cytoplasmic membrane [31], whereas HM-1, from Williopsis mrakii, kills sensitive cells presumably by interfering with b-(1 ! 3)-glucan synthesis [32].…”

The Biology of Pichia membranifaciens Killer Toxins

“…In short, the killing of action of PMKT, as well as several other yeast killer toxins, is related to peptide membrane permeation properties [16,41,125], whereas the mechanism of PMKT2 is related to cell cycle arrest [42]. …”

“…Furthermore, Pichia acaciae , Kluyveromyces lactis and Debaryomyces robertsiae cytoplasmic virus like elements encode toxic anticodon nucleases along with specific proteins that confer toxin immunity [13,14]. The potential use of killer yeasts and their toxins has been intended for various fields of application such as the alcohol fermentation industries (brewery, winery, and distillery), fermented vegetables, biological control of post-harvest diseases, yeast bio-typing, as antimycotics in the medical field and they have been used as model systems to understand eukaryotic polypeptide processing and expression of eukaryotic viruses [10,11,12,13,14,15,16,17,18,19,20,21]. …”