The viral killer system in yeast: from molecular biology to application

Abstract

Since the initial discovery of the yeast killer system almost 40 years ago, intensive studies have substantially strengthened our knowledge in many areas of biology and provided deeper insights into basic aspects of eukaryotic cell biology as well as into virus-host cell interactions and general yeast virology. Analysis of killer toxin structure, synthesis and secretion has fostered understanding of essential cellular mechanisms such as post-translational prepro-protein processing in the secretory pathway. Furthermore, investigation of the receptor-mediated mode of toxin action proved to be an effective means for dissecting the molecular structure and in vivo assembly of yeast and fungal cell walls, providing important insights relevant to combating infections by human pathogenic yeasts. Besides their general importance in understanding eukaryotic cell biology, killer yeasts, killer toxins and killer viruses are also becoming increasingly interesting with respect to possible applications in biomedicine and gene technology. This review will try to address all these aspects.

Killer-sensitive coexistence in metapopulations of micro-organisms

“…The excretion of antimicrobial compounds effective against related species or conspecifics is known to be widespread among bacteria (Chao & Levin 1981;Dykes 1995;Riley 1998) and yeasts (Tipper & Bostian 1984;Starmer et al 1987;Jacobs & Van Vuuren 1990;Abranches et al 1997;Schmitt & Breinig 2002). In mycelial fungi, somewhat comparable phenomena occur in the form of hyphal interference between different species (Berdy 1974).…”

“…The best-known killer system in S. cerevisiae is controlled by two separate multi-copy dsRNA virus-like particles in the cytoplasm (Schmitt & Breinig 2002). The genetic backgrounds of bacteriocin production and yeast killing are different, but their effects are very similar in ecological terms: the toxin produced eliminates competitor strains from the habitat.…”

Bacteriocins, spite and virulence

“…Furthermore, our predictions are not limited to bacteriocin production by bacteria. A variety of microbes, including yeasts (see Schmitt & Breinig 2002) and halophilic archea (see Cheung et al 1997) are known to produce toxins that tend to target conspecifics.…”

Mycoviruses: future therapeutic agents of invasive fungal infections in humans?

“…Although a filamentous basidiomycete fungus, Ustilago maydis, is known to secrete killer toxins encoded by cytoplasmic dsRNA mycoviruses that are lethal to mycovirus-free susceptible strains of the same fungus [37][38][39] [10,40]. In contrast to the S. cerevisiae toxins, killer toxins of nonSaccharomyces yeasts and especially those secreted by virus-infected killer strains of the yeasts H. uvarum and Z. bailii show a broad-spectrum antimycotic potential to human pathogenic strains, such as Candida albicans, Sporothrix schenkii, and Fusarium sp.…”

“…These derivatives have shown activity against various human fungal pathogenic fungi including C. albicans and may be therapeutic when administered parentally. For reviews of killer toxin/antibodies the reader is referred to Marquina et al [49], Magliani et al [55], and Schmitt and Breinig [40].…”