A killer yeast is a yeast, such as certain strains of Saccharomyces cerevisiae, that is able to secrete one of a number of toxic proteins lethal to susceptible cells of their own or similar species. The "killer toxins" are polypeptides that often function by creating pores in the cell membranes of the target. The yeast cells that produce the protein are intrinsically immune to its effects. 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 the 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.
In Saccharomyces cerevisiae The best-characterized toxin system is from a strain of Saccharomyces cerevisiae that was found to spoil brewing of beer. It encodes toxins by a double-stranded RNA virus that are translated to a precursor protein, cleaved and secreted outside of the cells, where they may affect susceptible yeast. Other killer systems can exist in S. cerevisiae, such as KHR1 and KHS1 genes encoded on chromosomes IX and V, respectively.
RNA virus
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, but spreads between cells during yeast mating. The family of Totiviridae in general helps M-type dsRNAs in a wide variety of yeasts.
Toxins
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. There are numerous apparently unrelated M dsRNAs, their only similarity being their genome and preprotoxin organization. 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.
Immunity 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.
Breinig, Sendzik, Eisfeld and Schmitt (2006) showed that K28 toxin is neutralized in toxin-expressing cells by the α chain in the cytosol, which has not yet been fully processed and still contains part of a γ chain attached to the C terminus. The uncleaved α chain neutralizes the K28 toxin by forming a complex with it.
In Kluyveromyces lactis Killer properties in Kluyveromyces lactis are associated with linear DNA plasmids, which have on their 5'end associated proteins, which enable them to replicate themselves in a way similar to adenoviruses. It is an example of protein priming in DNA replication. MAK genes are not known. The toxin consists of three subunits, which are matured in golgi complex by signal peptidase and glycosylated. The mechanism of action appears to be the inhibition of adenylate cyclase in sensitive cells. Affected cells are arrested in G1 phase and lose viability.
In other yeasts Toxin systems are found in some other yeasts:
Pichia and Williopsis Hanseniaspora uvarum Zygosaccharomyces bailii Ustilago maydis, a smut fungus that produces toxins of the killer toxin Kp4 family. Debaryomyces hansenii
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