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Exploring the Lethal Arsenal of Killer Yeasts for Biotechnology & Beyond

Yeasts, long recognized for their roles in the study of fundamental biological processes, as well as industrial fermentations and biotechnology, are also capable of producing potent antifungal proteins known as “killer toxins.” Our study of >1,000 strains of S. cerevisiae found that 50% produce these toxins and that many natural environments harbor these killer yeasts. This large and diverse collection of killer yeasts has led to the identification of novel toxins that effectively inhibit the growth of medically and commercially relevant fungal species. Notably, the opportunistic pathogen Candida glabrata (syn. Nakaseomyces glabratus) is uniquely susceptible to killer toxins produced by Saccharomyces yeasts. This susceptibility allowed the investigation of the evolution of toxin resistance. We discovered that K1 toxin-resistant clones displayed no significant changes in growth or morphology but had heightened sensitivity to detergents and were less virulent. Whole-genome sequencing revealed new genes involved in killer toxin resistance, many of which are linked to key processes such as vesicular trafficking and cell wall formation. Molecular modeling studies have also identified yeast killer toxins in C. glabrata that have structural homology to bacterial virulence factors, raising questions about their role in human disease. ��This research enhances our understanding of the molecular mechanisms of killer toxin resistance and intoxication, providing insights into their future applications and potential to exacerbate human disease.