An analog to digital converter controls bistable transfer competence of a widespread integrative and conjugative element
Abstract
Conjugative transfer of the integrative and conjugative element ICEclc in Pseudomonas requires development of a transfer competence state in stationary phase, which arises only in 3-5% of individual cells. The mechanisms controlling this bistable switch between non-active and transfer competent cells have long remained enigmatic. Using a variety of genetic tools and epistasis experiments in P. putida, we uncovered an 'upstream' cascade of three consecutive transcription factor-nodes, which controls transfer competence initiation. One of the uncovered transcription factors (named BisR) is representative for a new regulator family. Initiation activates a feedback loop, controlled by a second hitherto unrecognized heteromeric transcription factor named BisDC. Stochastic modeling and experimental data demonstrated the feedback loop to act as a scalable converter of unimodal (population-wide or 'analog') input to bistable (subpopulation-specific or ‘digital’) output. The feedback loop further enables prolonged production of BisDC, which ensures expression of the 'downstream' functions mediating ICE transfer competence in activated cells. Phylogenetic analyses showed that the ICEclc regulatory constellation with BisR and BisDC is widespread among Gamma- and Beta-proteobacteria, including various pathogenic strains, highlighting its evolutionary conservation and prime importance to control the behaviour of this wide family of conjugative elements.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided.
Article and author information
Author details
Funding
Swiss National Science Foundation (31003A_175638)
- Jan Roelof van der Meer
SystemsX.ch (Interdisciplinary Grant)
- Christian Mazza
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Carraro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.