The signal sequence of yeast killer toxin K2 confers producer self-protection and allows conversion into a modular toxin-antitoxin system

This is the authors' abstract. We don't add key points for this paper.

Some antimicrobial proteins secreted by yeast, known as yeast killer toxins, also target the producer species itself, necessitating a means of self-protection. Intriguingly, the M2 dsRNA killer virus in Saccharomyces cerevisiae contains a single open reading frame (ORF) that encodes both the pore-forming killer toxin K2 as well as a cognate immunity factor. Here, a systematic deletion screen reveals that expression of a 49-amino acid N-terminal peptide from this ORF is both necessary and sufficient for immunity and that the K2 toxin and this 49-residue immunity peptide can be functionally split into a modular toxin-antitoxin system. Further, the immunity peptide exhibits characteristics of a signal peptide and we thus propose that the K2 signal peptide serves a dual function: 1) Toxin targeting into the secretory pathway, and 2) establishing self-protective immunity. This case further implies that (signal) peptides form a potential source for antimicrobial resistance.