An analog to digital converter controls bistable transfer competence development of a widespread bacterial integrative and conjugative element
| Autor: | Xavier Richard, Nicolas Carraro, François Delavat, Christian Mazza, Sandra Sulser, Jan Roelof van der Meer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Bistability Gene Transfer Horizontal Computer science QH301-705.5 Science 030106 microbiology Regulator Genomics Computational biology General Biochemistry Genetics and Molecular Biology Conserved sequence 03 medical and health sciences Pseudomonas forward feedback loop Biology (General) Transcription factor 030304 developmental biology 0303 health sciences Microbiology and Infectious Disease Bacteria/genetics Bacterial Outer Membrane Proteins/genetics Bacterial Outer Membrane Proteins/metabolism Conjugation Genetic/physiology DNA Transposable Elements Gene Expression Regulation Bacterial Genome Bacterial Pseudomonas/genetics Pseudomonas/metabolism Transcription Factors/metabolism Pseudomonas putida clc element conjugation genetics genomics horizontal gene transfer infectious disease microbiology transfer competence General Immunology and Microbiology Bacteria 030306 microbiology General Neuroscience Genetics and Genomics General Medicine Feedback loop 030104 developmental biology Conjugation Genetic Horizontal gene transfer Epistasis Medicine Other Research Article Bacterial Outer Membrane Proteins Transcription Factors |
| Zdroj: | eLife, Vol 9 (2020) eLife eLife, vol. 9, pp. e57915 |
| Popis: | 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 modelling 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. eLife digest Mobile DNA elements are pieces of genetic material that can jump from one bacterium to another, and even across species. They are often useful to their host, for example carrying genes that allow bacteria to resist antibiotics. One example of bacterial mobile DNA is the ICEclc element. Usually, ICEclc sits passively within the bacterium’s own DNA, but in a small number of cells, it takes over, hijacking its host to multiply and to get transferred to other bacteria. Cells that can pass on the elements cannot divide, and so this ability is ultimately harmful to individual bacteria. Carrying ICEclc can therefore be positive for a bacterium but passing it on is not in the cell’s best interest. On the other hand, mobile DNAs like ICEclc have evolved to be disseminated as efficiently as possible. To shed more light on this tense relationship, Carraro et al. set out to identify the molecular mechanisms ICEclc deploys to control its host. Experiments using mutant bacteria revealed that for ICEclc to successfully take over the cell, a number of proteins needed to be produced in the correct order. In particular, a protein called BisDC triggers a mechanism to make more of itself, creating a self-reinforcing ‘feedback loop’. Mathematical simulations of the feedback loop showed that it could result in two potential outcomes for the cell. In most of the ‘virtual cells’, ICEclc ultimately remained passive; however, in a few, ICEclc managed to take over its hosts. In this case, the feedback loop ensured that there was always enough BisDC to maintain ICEclc’s control over the cell. Further analyses suggested that this feedback mechanism is also common in many other mobile DNA elements, including some that help bacteria to resist drugs. These results are an important contribution to understand how mobile DNAs manipulate their bacterial host in order to propagate and disperse. In the future, this knowledge could help develop new strategies to combat the spread of antibiotic resistance. |
| Databáze: | OpenAIRE |
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