Autotoxin-mediated latecomer killing in yeast communities

PLoS Biol. 2022 Nov 7;20(11):e3001844. doi: 10.1371/journal.pbio.3001844. eCollection 2022 Nov.

Abstract

Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Germ Cells
  • Glucose
  • Humans
  • Saccharomyces cerevisiae* / genetics
  • Yeast, Dried*

Substances

  • Glucose

Grants and funding

This work was partially supported by the Ohsumi Frontier Science Foundation (https://www.ofsf.or.jp/), the Basic Science Research Projects of Sumitomo Foundation (http://www.sumitomo.or.jp/e/), Japan Society for the Promotion of Science (JSPS) (https://www.jsps.go.jp/english/) KAKENHI (19K16070) to A.H.O., by JSPS KAKENHI (17H06386) to K.K., by JSPS KAKENHI (20H04862) to T.S.H., by Japan Science and Technology Agency (JST) (https://www.jst.go.jp/EN/) CREST, Japan, Grant Number JPMJCR18S3, Japan Agency for Medical Research and Development (AMED) (https://www.amed.go.jp/en/) Grant Number JP20wm0325003 to K.O. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.