An extremely poor nutritional condition enables efficient white cell mating in .

Pathogenic fungi employ diverse strategies to undergo sexual reproduction. It was previously believed that the major human fungal pathogen must switch from the "sterile" white state to the mating-competent opaque state to mate. We recently reported that glucose depletion could induce white cell mating at a moderate frequency. In this study, we demonstrate that white cells can undergo efficient mating when incubated on agar medium (water and agar, without additional nutritional components). Cell survival assays revealed that a subpopulation of white cells underwent cell death, releasing nutritional components that supported surviving cells in undergoing morphological changes and efficient mating. Inactivation of , , , and -genes required for cell death and reactive oxygen species generation in -resulted in a significant reduction in mating frequency under nutrient-depleted conditions. Taken together, our findings suggest that extremely poor nutritional conditions are able to promote epigenetic switch-independent mating in .By demonstrating that white cells can mate under nutrient-depleted conditions, the research uncovers a novel mechanism of sexual reproduction in this pathogenic fungus. The findings suggest that cell death, through the release of nutritional components and the generation of reactive oxygen species, plays a crucial role in facilitating mating under nutrient-depleted conditions. This research not only provides novel insights into the reproductive strategies of but also highlights potential avenues for exploring altruistic behaviors in other microorganisms. Understanding these mechanisms could have significant implications for the development of new therapeutic strategies to combat fungal infections, particularly in environments where nutrient limitations are common.