Ratiometric population sensing by a pump-probe signaling system in Bacillus subtilis

Heiko Babel,Sonja Schulmeister,Gabriele Malengo,Pablo Naranjo-Meneses,Stephanie Trauth,Ilka B Bischofs,Victor Sourjik

doi:10.1038/s41467-020-14840-w

Abstract

Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations. Gram-positive bacteria frequently use signaling peptides, which are either detected at the cell surface or ‘probed’ by intracellular receptors after being pumped into the cytoplasm. While the former type is used to monitor cell density, the functions of pump-probe networks are less clear. Here we show that pump-probe networks can, in principle, perform different tasks and mediate quorum-sensing, chronometric and ratiometric control. We characterize the properties of the prototypical PhrA-RapA system in Bacillus subtilis using FRET. We find that changes in extracellular PhrA concentrations are tracked rather poorly; instead, cells accumulate and strongly amplify the signal in a dose-dependent manner. This suggests that the PhrA-RapA system, and others like it, have evolved to sense changes in the composition of heterogeneous populations and infer the fraction of signal-producing cells in a mixed population to coordinate cellular behaviors.

Highlights

Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations
RRNPP systems are widespread among Firmicutes and regulate traits which are commonly controlled by bacterial communication, such as cell differentiation, various forms of horizontal gene transfer, and the synthesis offactors that shape the interactions of these bacteria with other microbes and their hosts[2,3]
The defining features of a pump–probe network are that cells “pump” extracellular signaling molecules into the cytoplasm, effectively converting the extracellular into an intracellular signal, which is “probed“ by the appropriate intracellular receptor and transduced into a cellular output (Fig. 1a)

Summary

Introduction

Communication by means of diffusible signaling molecules facilitates higher-level organization of cellular populations. The systems-level functions that are performed by these signaling networks are still unclear They are commonly thought to facilitate “quorum sensing” in a bacterial population, i.e., the populationwide coordination of gene expression in response to changes in cell density[10,11]. They could function as sensitive devices for cell-density monitoring[12], but whether RRNPP signaling networks implement a “quorum-sensing” type of regulation has been questioned[13,14]. One of the best characterized pump–probe network is the PhrA-

Methods

Results

Conclusion