Altruistic feeding and cell-cell signaling during bacterial differentiation actively enhance phenotypic heterogeneity

bioRxiv [Preprint]. 2024 Mar 27:2024.03.27.587046. doi: 10.1101/2024.03.27.587046.

Abstract

Starvation triggers bacterial spore formation, a committed differentiation program that transforms a vegetative cell into a dormant spore. Cells in a population enter sporulation non-uniformly to secure against the possibility that favorable growth conditions, which puts sporulation-committed cells at a disadvantage, may resume. This heterogeneous behavior is initiated by a passive mechanism: stochastic activation of a master transcriptional regulator. Here, we identify a cell-cell communication pathway that actively promotes phenotypic heterogeneity, wherein Bacillus subtilis cells that start sporulating early utilize a calcineurin-like phosphoesterase to release glycerol, which simultaneously acts as a signaling molecule and a nutrient to delay non-sporulating cells from entering sporulation. This produced a more diverse population that was better poised to exploit a sudden influx of nutrients compared to those generating heterogeneity via stochastic gene expression alone. Although conflict systems are prevalent among microbes, genetically encoded cooperative behavior in unicellular organisms can evidently also boost inclusive fitness.

Publication types

  • Preprint

Grants and funding

This work was funded by the Intramural Research Program of the National Institutes of Health (NIH), the National Cancer Institute, the Center for Cancer Research (K.S.R.), the National Library of Medicine (L.A.), the National Institute of Diabetes and Digestive and Kidney Diseases (C.A.B.), the National Institute of Biomedical Imaging and Bioengineering (H.S.), and the Advanced Imaging and Microscopy Resource (J.C. and H.S.). This work utilized the NIH HPC Biowulf computer cluster (V.A. and L.A.). This work was supported by the Howard Hughes Medical Institute (HHMI) (H.S.). This article is subject to HHMI’s Open Access to Publications policy. HHMI laboratory heads have previously granted a non-exclusive CC BY 4.0 license to the public and a sub-licensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication.