Two novel XRE-like transcriptional regulators control phenotypic heterogeneity in Photorhabdus luminescens cell populations

Simone Eckstein,Michael Seidel,Mats Lechtenfeld,Ralf Heermann,Jannis Brehm

doi:10.1186/s12866-021-02116-2

Simone Eckstein, Michael Seidel + Show 3 more

Open Access

https://doi.org/10.1186/s12866-021-02116-2

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Abstract

BackgroundThe insect pathogenic bacterium Photorhabdus luminescens exists in two phenotypically different forms, designated as primary (1°) and secondary (2°) cells. Upon yet unknown environmental stimuli up to 50% of the 1° cells convert to 2° cells. Among others, one important difference between the phenotypic forms is that 2° cells are unable to live in symbiosis with their partner nematodes, and therefore are not able to re-associate with them. As 100% switching of 1° to 2° cells of the population would lead to a break-down of the bacteria’s life cycle the switching process must be tightly controlled. However, the regulation mechanism of phenotypic switching is still puzzling.ResultsHere we describe two novel XRE family transcriptional regulators, XreR1 and XreR2, that play a major role in the phenotypic switching process of P. luminescens. Deletion of xreR1 in 1° or xreR2 in 2° cells as well as insertion of extra copies of xreR1 into 2° or xreR2 into 1° cells, respectively, induced the opposite phenotype in either 1° or 2° cells. Furthermore, both regulators specifically bind to different promoter regions putatively fulfilling a positive autoregulation. We found initial evidence that XreR1 and XreR2 constitute an epigenetic switch, whereby XreR1 represses xreR2 expression and XreR2 self-reinforces its own gene by binding to XreR1.ConclusionRegulation of gene expression by the two novel XRE-type regulators XreR1 and XreR2 as well as their interplay represents a major regulatory process in phenotypic switching of P. luminescens. A fine-tuning balance between both regulators might therefore define the fate of single cells to convert from the 1° to the 2° phenotype.

Highlights

The insect pathogenic bacterium Photorhabdus luminescens exists in two phenotypically different forms, designated as primary (1°) and secondary (2°) cells
These properties include the biosynthesis of secondary metabolites like antibiotics or production of anthraquinones, which results in reddishbrown pigmentation, as well as bioluminescence or the formation of crystalline inclusion proteins, cell clumps and mucoid colony morphology [3,4,5,6,7]
While both cell forms are pathogenic towards insects, 2° cells are not able to re-associate with the nematodes after depletion of nutrients derived by the insect host [7, 8]

Summary

Introduction

The insect pathogenic bacterium Photorhabdus luminescens exists in two phenotypically different forms, designated as primary (1°) and secondary (2°) cells. The two cell forms are easy to distinguish as 1° cells exhibit specific phenotypic features that are absent in 2° cells These properties include the biosynthesis of secondary metabolites like antibiotics or production of anthraquinones, which results in reddishbrown pigmentation, as well as bioluminescence or the formation of crystalline inclusion proteins, cell clumps and mucoid colony morphology [3,4,5,6,7]. While both cell forms are pathogenic towards insects, 2° cells are not able to re-associate with the nematodes after depletion of nutrients derived by the insect host [7, 8]. The switch has only been observed unidirectional occurring from 1° to 2° cells suggesting that a key signal which is missing under laboratory conditions [11]

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