The bacterial cell cycle consists of a series of genetically coordinated biochemical and biophysical events. In Caulobacter crescentus , CtrA is an essential cell cycle regulator that modulates many cell cycle processes. In the present study, the role of the CtrA was investigated in Rhodobacter sphaeroides 2.4.1 by employing genetic, molecular, and bioinformatic approaches. Examination of the ctrA -null mutant revealed that the loss of CtrA did not affect growth characteristics and cell morphology in R. sphaeroides when grown under aerobic or photosynthetic growth conditions but slower growth was noticed in the anaerobic-dark-DMSO condition. Phylogenetic analyses demonstrated that CtrA has diversified its role in major lineages of α-Proteobacteria and has possibly been involved in adaptation to variable lifestyles. Analysis of the CtrA binding sites in the R. sphaeroides genome suggests that CtrA may regulate 127 genes involving different cellular processes. Protein homology searches revealed that only a small number of ctrA-regulated genes are homologous across C. crescentus , R. capsulatus , and R. sphaeroides . Comparison of the functions of putative ctrA-regulated genes in C. crescentus , R. capsulatus, and R. sphaeroides revealed that all three species possessed broad pathway control across a variety of cluster of orthologous gene functions (COGs). However, interestingly, it seems that the essentiality of CtrA in C. crescentus may depend more on the selective control that it exerts on a few critical cell cycle genes and pathways that are not controlled by CtrA in a similar fashion in R. capsulatus and R. sphaeroide s .
Huang, K.J. and Igo, M.M. (1996) Identification of the Bases in the OmpF Regulatory Region, Which Interact with the Transcription Factor OmpR. Journal of Molecular Biology, 262, 615-628. https://doi.org/10.1006/jmbi.1996.0540
Quon, K.C., Marczynski, G.T. and Shapiro, L. (1996) Cell Cycle Control by an Essential Bacterial Two-Component Signal Transduction Protein. Cell, 84, 83-93. https://doi.org/10.1016/S0092-8674(00)80995-2
Giovannoni, S.J., Tripp, H.J., Givan, S., Podar, M., Vergin, K.L., Baptista, D., Bibbs, L., Eads, J., Richardson, T.H., Noordewier, M., et al. (2005) Genome Streamlining in a Cosmopolitan Oceanic Bacterium. Science, 309, 1242-1245. https://doi.org/10.1126/science.1114057
Barnett, M.J., Hung, D.Y., Reisenauer, A., Shapiro, L. and Long, S.R. (2001) A Homolog of the CtrA Cell Cycle Regulator Is Present and Essential in Sinorhizobium meliloti. Journal of Bacteriology, 183, 3204-3210. https://doi.org/10.1128/JB.183.10.3204-3210.2001
Laub, M.T., Chen, S.L., Shapiro, L. and McAdams, H.H. (2002) Genes Directly Controlled by CtrA, a Master Regulator of the Caulobacter Cell Cycle. Proceedings of the National Academy of Sciences of USA, 99, 4632-4637. https://doi.org/10.1073/pnas.062065699
Laub, M.T., McAdams, H.H., Feldblyum, T., Fraser, C.M. and Shapiro, L. (2000) Global Analysis of the Genetic Network Controlling a Bacterial Cell Cycle. Science, 290, 2144-2148. https://doi.org/10.1126/science.290.5499.2144
Holtzendorff, J., Reinhardt, J. and Viollier, P.H. (2006) Cell Cycle Control by Oscillating Regulatory Proteins in Caulobacter crescentus. BioEssays, 28, 355-361. https://doi.org/10.1002/bies.20384
Domian, I.J., Reisenauer, A. and Shapiro, L. (1999) Feedback Control of a Master Bacterial Cell-Cycle Regulator. Proceedings of the National Academy of Sciences of USA, 96, 6648-6653. https://doi.org/10.1073/pnas.96.12.6648
Bellefontaine, A.F., Pierreux, C.E., Mertens, P., Vandenhaute, J., Letesson, J.J. and De Bolle, X. (2002) Plasticity of a Transcriptional Regulation Network among Alpha-Proteobacteria Is Supported by the Identification of CtrA Targets in Brucella abortus. Molecular Microbiology, 43, 945-960. https://doi.org/10.1046/j.1365-2958.2002.02777.x
McAdams, H.H., Srinivasan, B. and Arkin, A.P. (2004) The Evolution of Genetic Regulatory Systems in Bacteria. Nature Reviews Genetics, 5, 169-178. https://doi.org/10.1038/nrg1292
Andersson, S.G., Zomorodipour, A., Andersson, J.O., Sicheritz-Ponten, T., Alsmark, U.C., Podowski, R.M., Naslund, A.K., Eriksson, A.S., Winkler, H.H. and Kurland, C.G. (1998) The Genome Sequence of Rickettsia prowazekii and the Origin of Mitochondria. Nature, 396, 133-140. https://doi.org/10.1038/24094
Mercer, R.G., Callister, S.J., Lipton, M.S., Pasa-Tolic, L., Strnad, H., Paces, V., Beatty, J.T. and Lang, A.S. (2010) Loss of the Response Regulator CtrA Causes Pleiotropic Effects on Gene Expression But Does Not Affect Growth Phase Regulation in Rhodobacter capsulatus. Journal of Bacteriology, 192, 2701-2710. https://doi.org/10.1128/JB.00160-10
Lang, A.S. and Beatty, J.T. (2000) Genetic Analysis of a Bacterial Genetic Exchange Element: The Gene Transfer Agent of Rhodobacter capsulatus. Proceedings of the National Academy of Sciences of USA, 97, 859-864. https://doi.org/10.1073/pnas.97.2.859
Miller, T.R. and Belas, R. (2006) Motility Is Involved in Silicibacter sp. TM1040 Interaction with Dinoflagellates. Environmental Microbiology, 8, 1648-1659. https://doi.org/10.1111/j.1462-2920.2006.01071.x
Lang, A.S. and Beatty, J.T. (2002) A Bacterial Signal Transduction System Controls Genetic Exchange and Motility. Journal of Bacteriology, 184, 913-918. https://doi.org/10.1128/jb.184.4.913-918.2002
Kiley, P.J. and Kaplan, S. (1988) Molecular Genetics of Photosynthetic Membrane Biosynthesis in Rhodobacter sphaeroides. Microbiological Reviews, 52, 50-69.
Suwanto, A. and Kaplan, S. (1989) Physical and Genetic Mapping of the Rhodobacter sphaeroides 2.4.1 Genome: Presence of Two Unique Circular Chromosomes. Journal of Bacteriology, 171, 5850-5859. https://doi.org/10.1128/jb.171.11.5850-5859.1989
Sistrom, W.R. (1960) A Requirement for Sodium in the Growth of Rhodopseudomonas spheroides. Journal of General Microbiology, 22, 778-785. https://doi.org/10.1099/00221287-22-3-778
Oh, J.I. and Kaplan, S. (1999) The cbb3 Terminal Oxidase of Rhodobacter sphaeroides 2.4.1: Structural and Functional Implications for the Regulation of Spectral Complex Formation. Biochem, 38, 2688-2696. https://doi.org/10.1021/bi9825100
Lenz, O., Schwartz, E., Dernedde, J., Eitinger, M. and Friedrich, B. (1994) The Alcaligenes eutrophus H16 hoxX Gene Participates in Hydrogenase Regulation. Journal of Bacteriology, 176, 4385-4393. https://doi.org/10.1128/jb.176.14.4385-4393.1994
Steinmetz, M., Le Coq, D., Aymerich, S., Gonzy-Treboul, G. and Gay, P. (1985) The DNA Sequence for the Secreted Bacillus subtilis Enzyme Levansucrase. Molecular Genetics and Genomics, 200, 220-228. https://doi.org/10.1007/BF00425427
Davis, J., Donohue, T.J. and Kaplan, S. (1988) Construction, Characterization, and Complementation of Puf Mutant of Rhodobacter sphaeroides. Journal of Bacteriology, 170, 320-329. https://doi.org/10.1128/jb.170.1.320-329.1988
Tai, T.N., Moore, M.D. and Kaplan, S. (1988) Cloning and Characterization of the 5-Aminolevulinic Synthase Gene(s) from Rhodobacter sphaeroides. Gene, 70, 139-151. https://doi.org/10.1016/0378-1119(88)90112-6
Gay, P., Le Coq, D., Steinmetz, M., Berkelman, T. and Kado, C.I. (1985) Positive Selection Procedure for Entrapment of Insertion Sequence Elements in Gram-Negative Bacteria. Journal of Bacteriology, 164, 918-921.
Livak, K.J. and Schmittgen, T.D. (2001) Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-408. https://doi.org/10.1006/meth.2001.1262
Sockett, R.E., Armitage, J.P. and Evans, M.C. (1987) Methylation-Independent and Methylation-Dependent Chemotaxis in Rhodobacter sphaeroides and Rhodospirillum rubrum. Journal of Bacteriology, 169, 5808-5814. https://doi.org/10.1128/jb.169.12.5808-5814.1987
Poggio, S., Abreu-Goodger, C., Fabela, S., Osorio, A., Dreyfus, G., Vinuesa, P. and Camarena, L. (2007) A Complete Set of Flagellar Genes Acquired by Horizontal Transfer Coexists with the Endogenous Flagellar System in Rhodobacter sphaeroides. Journal of Bacteriology, 189, 3208-3216. https://doi.org/10.1128/JB.01681-06
De la Mora, J., Ballado, T., Gonzalez-Pedrajo, B., Camarena, L. and Dreyfus, G. (2007) The Flagellar Muramidase from the Photosynthetic Bacterium Rhodobacter sphaeroides. Journal of Bacteriology, 189, 7998-8004. https://doi.org/10.1128/JB.01073-07
Edgar, R.C. (2004) MUSCLE: Multiple Sequence Alignment with High Accuracy and High Throughput. Nucleic Acids Research, 32, 1792-1797. https://doi.org/10.1093/nar/gkh340
Guindon, S. and Gascuel, O. (2003) A Simple, Fast and Accurate Algorithm to Estimate Large Phylogenies by Maximum Likelihood. Systematic Biology, 52, 696-704. https://doi.org/10.1080/10635150390235520
Jones, D.T., Taylor, W.R. and Thornton, J.M. (1992) The Rapid Generation of Mutation Data Matrices from Protein Sequences. Computer Applications in the Biosciences, 8, 275-282.
Bailey, T.L. and Elkan, C. (1994) Fitting a Mixture Model by Expectation Maximization to Discover Motifs in Biopolymers. In: Proceedings of the 2nd International Conference on Intelligent Systems for Molecular Biology, AAAI Press, Menlo Park, 28-36.
Bailey, T.L. and Gribskov, M. (1998) Combining Evidence Using P-Values: Application to Sequence Homology Searches. Bioinformatics, 14, 48-54. https://doi.org/10.1093/bioinformatics/14.1.48
Tatusov, R.L., Fedorova, N.D., Jackson, J.D., Jacobs, A.R., Kiryutin, B., Koonin, E.V., Krylov, D.M., Mazumder, R., Mekhedov, S.L., Nikolskaya, A.N., et al. (2003) The COG Database: An Updated Version Includes Eukaryotes. BMC Bioinformatics, 4, 41. https://doi.org/10.1186/1471-2105-4-41
Tatusov, R.L., Koonin, E.V. and Lipman, D.J. (1997) A Genomic Perspective on Protein Families. Science, 278, 631-637. https://doi.org/10.1126/science.278.5338.631
Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W. and Lipman, D.J. (1997) Gapped BLAST and PSI-BLAST: A New Generation of Protein Database Search Programs. Nucleic Acids Research, 25, 3389-3402. https://doi.org/10.1093/nar/25.17.3389
Brilli, M., Fondi, M., Fani, R., Mengoni, A., Ferri, L., Bazzicalupo, M. and Biondi, E.G. (2010) The Diversity and Evolution of Cell Cycle Regulation in Alpha-Proteobacteria: A Comparative Genomic Analysis. BMC Systematic Biology, 4, 52. https://doi.org/10.1186/1752-0509-4-52
Hallez, R., Bellefontaine, A.F., Letesson, J.J. and De Bolle, X. (2004) Morphological and Functional Asymmetry in Alpha-Proteobacteria. Trends in Microbiology, 12, 361-365. https://doi.org/10.1016/j.tim.2004.06.002
Sockett, R.E., Foster, J.C.A. and Armitage, J.P. (1990) Molecular Biology of the Rhodobacter sphaeroides Flagellum. In: Drews, G. and Dawes, E.A., Eds., Molecular Biology of Membrane-Bound Complexes in Phototrophic Bacteria, Springer, Berlin, No. 53, 473-479.