**5. Conclusions**

In this study we show that regulation of the CtrA regulon, including traits related to phenotypic heterogeneity, is additionally controlled by the aerobic–anerobic regulators Crp/Fnr in *D. shibae* and by FnrL/RegA in *R. capsulatus*. This finding is especially important for the understanding of the metabolically flexible lifestyles of these bacteria. The analysis of the available transcriptomic datasets revealed multiple possible integration sites of the Crp/Fnr signal into the CtrA phosphorelay, but a final explanation is still elusive based on these data. Nevertheless, this investigation provides the first insights into the integration of a second environmental signal into the CtrA phosphorelay and demonstrates a strong transcriptional connection between QS, CtrA-regulated traits, and Crp/Fnr regulators in alphaproteobacteria, which has an interesting parallel with QS and Crp/Fnr regulators in a second class of proteobacteria. To our knowledge, *D. shibae* and *R. capsulatus* are the first two organisms where both Dnr and HNOX NO-sensor proteins have been studied. Further investigation is necessary to clarify the interaction between the CtrA phosphorelay and the Crp/Fnr regulators. For example, it would be helpful to confirm if an additional kinase is indeed regulating ChpT in these bacteria.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-2607/8/4/562/s1: Figure S1. Transcript level changes of *D. shibae* c-di-GMP signaling genes; Figure S2. Comparison of changes in transcript levels during different stages of the "Jekyll and Hyde" interaction between *Dinoroseobacter shibae* and the dinoflagellate *Prorocentrum minimum*; Figure S3. Transcript level changes of various FnrL- and RegA-related genes in CtrA phosphorelay mutants during exponential and stationary phases of growth in *Rhodobacter capsulatus*; Table S1. Assignment of genes into functional categories.

**Author Contributions:** Conceptualization, S.K.; methodology, formal analysis, and data curation S.K.; writing—original draft preparation, S.K.; writing—review and editing, A.S.L.; visualization, S.K.; supervision, A.S.L.; funding acquisition, A.S.L. All authors have read and agree to the published version of the manuscript.

**Funding:** This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) (grant number 341561 to A.S.L.). S.K. was supported in part by funding from the Memorial University of Newfoundland School of Graduate Studies.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
