Killer yeast

A killer yeast is a yeast, such as Saccharomyces cerevisiae, which is able to secrete one of a number of toxic proteins which are lethal to susceptible cells. These 'killer toxins' are polypeptides that kill sensitive cells of the same or related species, often functioning by creating pores in target cell membranes. The phenomenon was first observed by Louis Pasteur, as noted in 1877. These yeast cells are immune to the toxic effects of the protein due to an intrinsic immunity. Killer yeast strains can be a problem in commercial processing because they can kill desirable strains. The killer yeast system was first described in 1963. Study of killer toxins helped to better understand the secretion pathway of yeast, which is similar to those of more complex eukaryotes. It also can be used in treatment of some diseases, mainly those caused by fungi. A killer yeast is a yeast, such as Saccharomyces cerevisiae, which is able to secrete one of a number of toxic proteins which are lethal to susceptible cells. These 'killer toxins' are polypeptides that kill sensitive cells of the same or related species, often functioning by creating pores in target cell membranes. The phenomenon was first observed by Louis Pasteur, as noted in 1877. These yeast cells are immune to the toxic effects of the protein due to an intrinsic immunity. Killer yeast strains can be a problem in commercial processing because they can kill desirable strains. The killer yeast system was first described in 1963. Study of killer toxins helped to better understand the secretion pathway of yeast, which is similar to those of more complex eukaryotes. It also can be used in treatment of some diseases, mainly those caused by fungi. The best characterized toxin system is from yeast (Saccharomyces cerevisiae), which was found to spoil brewing of beer. In S. cerevisiae are toxins encoded by a double-stranded RNA virus, translated to a precursor protein, cleaved and secreted outside of the cells, where they may affect susceptible yeast.There are other killer systems in S. cerevisiae, such as KHR1 and KHS1 genes encoded on chromosomes IX and V, respectively. The virus, L-A, is an icosahedral virus of S. cerevisiae comprising a 4.6 kb genomic segment and several satellite double-stranded RNA sequences, called M dsRNAs. The genomic segment encodes for the viral coat protein and a protein which replicates the viral genomes. The M dsRNAs encode the toxin, of which there are at least three variants in S. cerevisiae, and many more variants across all species. L-A virus uses yeast Ski complex (super killer) and MAK (maintenance of killer) chromosomal genes for its preservation in the cell. The virus is not released into the environment. It spreads between cells during yeast mating. The initial protein product from translation of the M dsRNA is called the preprotoxin, which is targeted to the yeast secretory pathway. The preprotoxin is processed and cleaved to produce an α/β dimer, which is the active form of the toxin, and is released into the environment. The two most studied variant toxins in S. cerevisiae are K1 and K28. K1 binds to the β-1,6-D-glucan receptor on the target cell wall, moves inside, and then binds to the plasma membrane receptor Kre1p. It forms a cation-selective ion channel in the membrane, which is lethal to the cell. K28 uses the α-1,6-mannoprotein receptor to enter the cell, and utilizes the secretory pathway in reverse by displaying the endoplasmic reticulum HDEL signal. From the ER, K28 moves into the cytoplasm and shuts down DNA synthesis in the nucleus, triggering apoptosis. Sesti, Shih, Nikolaeva and Goldstein (2001) claimed that K1 inhibits the TOK1 membrane potassium channel before secretion, and although the toxin reenters through the cell wall it is unable to reactivate TOK1. However Breinig, Tipper and Schmitt (2002) showed that the TOK1 channel was not the primary receptor for K1, and that TOK1 inhibition does not confer immunity. Vališ, Mašek, Novotná, Pospíšek and Janderová (2006) experimented with mutants which produce K1 but do not have immunity to it, and suggested that cell membrane receptors were being degraded in the secretion pathway of immune cells, apparently due to the actions of unprocessed α chains.