Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Bacterial protein networks: properties and functions

Nature Reviews Microbiology volume 13, pages 559–572 (2015)Cite this article

Subjects

Key Points

  • In bacteria, as in eukaryotes, networks of physical interactions among proteins are at the core of all cellular processes, enabling cells to execute diverse complex functions in a concerted and coordinated manner.

  • Fuelled by a number of genetic, biochemical and fluorescence-based techniques, our ability to map bacterial protein networks and to investigate their functions has increased dramatically in recent years.

  • The diversity, lower complexity and evolutionary age of bacterial protein networks make them excellent models for the investigation of general architectural principles — such as hub-dominated structures — that are conserved in network evolution, as well as deviations from these principles.

  • Many bacterial protein networks share common properties, such as modularity, plasticity, crosstalk and robustness, which manifest at multiple levels.

  • Well-studied protein networks that control chemotaxis and the cell cycle in Escherichia coli exemplify how analyses of network structure and function lead to a better understanding of cellular processes in bacteria.

Abstract

Distinct cellular functions are executed by separate groups of proteins, organized into complexes or functional modules, which are ultimately interconnected in cell-wide protein networks. Understanding the structures and operational modes of these networks is one of the next great challenges in biology, and microorganisms are at the forefront of research in this field. In this Review, we present our current understanding of bacterial protein networks, their general properties and the tools that are used for systematically mapping and characterizing them. We then discuss two well-studied examples, the chemotaxis network and the cell cycle network in Escherichia coli, to illustrate how network architecture promotes function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Properties of protein networks.
Figure 2: Structure and properties of the chemotaxis network.
Figure 3: Network of interactions among chemotaxis and flagellar-motor proteins.
Figure 4: The cell cycle protein network.
Figure 5: Crosstalk between the elongation complex and the divisome.

Similar content being viewed by others

References

  1. Nguyen, C. et al. Trapping the dynamic acyl carrier protein in fatty acid biosynthesis. Nature 505, 427–431 (2014).

    CAS  PubMed  Google Scholar 

  2. Bandyra, K. J., Bouvier, M., Carpousis, A. J. & Luisi, B. F. The social fabric of the RNA degradosome. Biochim. Biophys. Acta 1829, 514–522 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Agapakis, C. M., Boyle, P. M. & Silver, P. A. Natural strategies for the spatial optimization of metabolism in synthetic biology. Nat. Chem. Biol. 8, 527–535 (2012).

    CAS  PubMed  Google Scholar 

  4. Castellana, M. et al. Enzyme clustering accelerates processing of intermediates through metabolic channeling. Nat. Biotech. 32, 1011–1018 (2014).

    CAS  Google Scholar 

  5. Stinson, B. M. et al. Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine. Cell 153, 628–639 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Rain, J. C. et al. The protein–protein interaction map of Helicobacter pylori. Nature 409, 211–215 (2001).

    CAS  PubMed  Google Scholar 

  7. Butland, G. et al. Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature 433, 531–537 (2005). This article reports the first global AP–MS PPI screen in E. coli.

    CAS  PubMed  Google Scholar 

  8. Parrish, J. R. et al. A proteome-wide protein interaction map for Campylobacter jejuni. Genome Biol. 8, R130 (2007).

    PubMed  PubMed Central  Google Scholar 

  9. Sato, S. et al. A large-scale protein–protein interaction analysis in Synechocystis sp. PCC6803. DNA Res. 14, 207–216 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Shimoda, Y. et al. A large scale analysis of protein–protein interactions in the nitrogen-fixing bacterium Mesorhizobium loti. DNA Res. 15, 13–23 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Titz, B. et al. The binary protein interactome of Treponema pallidum — the syphilis spirochete. PLoS ONE 3, e2292 (2008).

    PubMed  PubMed Central  Google Scholar 

  12. Hu, P. et al. Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins. PLoS Biol. 7, e96 (2009).

    PubMed  Google Scholar 

  13. Kuhner, S. et al. Proteome organization in a genome-reduced bacterium. Science 326, 1235–1240 (2009).

    PubMed  Google Scholar 

  14. Rajagopala, S. V. et al. The binary protein–protein interaction landscape of Escherichia coli. Nat. Biotech. 32, 285–290 (2014). This paper details the first global Y2H screen in E. coli.

    CAS  Google Scholar 

  15. Rajagopala, S. V. et al. The protein network of bacterial motility. Mol. Syst. Biol. 3, 128 (2007).

    PubMed  PubMed Central  Google Scholar 

  16. Kentner, D. & Sourjik, V. Dynamic map of protein interactions in the Escherichia coli chemotaxis pathway. Mol. Syst. Biol. 5, 238 (2009). This study provides the first example of a network-wide PPI analysis in bacteria using FRET.

    PubMed  PubMed Central  Google Scholar 

  17. Li, H. & Sourjik, V. Assembly and stability of flagellar motor in Escherichia coli. Mol. Microbiol. 80, 886–899 (2011).

    CAS  PubMed  Google Scholar 

  18. Kumar, M. & Sourjik, V. Physical map and dynamics of the chaperone network in Escherichia coli. Mol. Microbiol. 84, 736–747 (2012).

    CAS  PubMed  Google Scholar 

  19. Karimova, G., Dautin, N. & Ladant, D. Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis. J. Bacteriol. 187, 2233–2243 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Alexeeva, S. et al. Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET. Mol. Microbiol. 77, 384–398 (2010).

    CAS  PubMed  Google Scholar 

  21. Yamada, T. & Bork, P. Evolution of biomolecular networks: lessons from metabolic and protein interactions. Nat. Rev. Mol. Cell Biol. 10, 791–803 (2009).

    CAS  PubMed  Google Scholar 

  22. Fraser, H. B., Hirsh, A. E., Steinmetz, L. M., Scharfe, C. & Feldman, M. W. Evolutionary rate in the protein interaction network. Science 296, 750–752 (2002).

    CAS  PubMed  Google Scholar 

  23. Han, J. D. et al. Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430, 88–93 (2004).

    CAS  PubMed  Google Scholar 

  24. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. From molecular to modular cell biology. Nature 402, C47–C52 (1999). This fundamental article defines the concept of modularity in cell biology.

    CAS  PubMed  Google Scholar 

  25. Wagner, G. P., Pavlicev, M. & Cheverud, J. M. The road to modularity. Nat. Rev. Genet. 8, 921–931 (2007).

    CAS  PubMed  Google Scholar 

  26. Ryan, C. J. et al. Hierarchical modularity and the evolution of genetic interactomes across species. Mol. Cell 46, 691–704 (2012). This investigation provides one of the first comprehensive cellular-network comparisons between two species of yeast.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Skerker, J. M. et al. Rewiring the specificity of two-component signal transduction systems. Cell 133, 1043–1054 (2008). This research demonstrates that the specificity of phosphorylation in two-component systems can be explained by a small set of co-evolved amino acids.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Goulian, M. Two-component signaling circuit structure and properties. Curr. Opin. Microbiol. 13, 184–189 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Townsend, G. E. II, Raghavan, V., Zwir, I. & Groisman, E. A. Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems. Proc. Natl Acad. Sci. USA 110, E161–E169 (2013).

    CAS  PubMed  Google Scholar 

  30. Noinaj, N., Guillier, M., Barnard, T. J. & Buchanan, S. K. TonB-dependent transporters: regulation, structure, and function. Annu. Rev. Microbiol. 64, 43–60 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wartel, M. et al. A versatile class of cell surface directional motors gives rise to gliding motility and sporulation in Myxococcus xanthus. PLoS Biol. 11, e1001728 (2013). This work shows that two cellular machineries operating at distinct cellular stages use the same core sub-module (the Agl motor) to be propelled around the cell periphery.

    PubMed  PubMed Central  Google Scholar 

  32. Spirin, V. & Mirny, L. A. Protein complexes and functional modules in molecular networks. Proc. Natl Acad. Sci. USA 100, 12123–12128 (2003).

    CAS  PubMed  Google Scholar 

  33. Roche, B. et al. Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity. Biochem. Biophys. Acta 1827, 455–469 (2013).

    CAS  PubMed  Google Scholar 

  34. Mohammadi, T. et al. The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli. Mol. Microbiol. 65, 1106–1121 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. White, C. L., Kitich, A. & Gober, J. W. Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD. Mol. Microbiol. 76, 616–633 (2010).

    CAS  PubMed  Google Scholar 

  36. Cameron, J. C., Wilson, S. C., Bernstein, S. L. & Kerfeld, C. A. Biogenesis of a bacterial organelle: the carboxysome assembly pathway. Cell 155, 1131–1140 (2013).

    CAS  PubMed  Google Scholar 

  37. Boehm, A. et al. Second messenger-mediated adjustment of bacterial swimming velocity. Cell 141, 107–116 (2010).

    CAS  PubMed  Google Scholar 

  38. Lee, T. K. et al. A dynamically assembled cell wall synthesis machinery buffers cell growth. Proc. Natl Acad. Sci. USA 111, 4554–4559 (2014). This study illustrates how dynamic PPIs can make a network more robust to fluctuations in its limiting components.

    CAS  PubMed  Google Scholar 

  39. Raj, A. & van Oudenaarden, A. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell 135, 216–226 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Eldar, A. & Elowitz, M. B. Functional roles for noise in genetic circuits. Nature 467, 167–173 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Elowitz, M. B., Levine, A. J., Siggia, E. D. & Swain, P. S. Stochastic gene expression in a single cell. Science 297, 1183–1186 (2002).

    CAS  PubMed  Google Scholar 

  42. Sanchez, A. & Golding, I. Genetic determinants and cellular constraints in noisy gene expression. Science 342, 1188–1193 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Jones, D. L., Brewster, R. C. & Phillips, R. Promoter architecture dictates cell-to-cell variability in gene expression. Science 346, 1533–1536 (2014). This article demonstrates that noise in gene expression in bacteria depends on promoter architecture.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Barkai, N. & Leibler, S. Robustness in simple biochemical networks. Nature 387, 913–917 (1997).

    CAS  PubMed  Google Scholar 

  45. Kollmann, M., Lovdok, L., Bartholome, K., Timmer, J. & Sourjik, V. Design principles of a bacterial signalling network. Nature 438, 504–507 (2005).

    CAS  PubMed  Google Scholar 

  46. Shinar, G., Milo, R., Martínez, M. R. & Alon, U. Input–output robustness in simple bacterial signaling systems. Proc. Natl Acad. Sci. USA 104, 19931–19935 (2007). This analysis proposes an elegant mechanism that can explain the robustness of two-component signalling against noise in gene expression.

    CAS  PubMed  Google Scholar 

  47. Oleksiuk, O. et al. Thermal robustness of signaling in bacterial chemotaxis. Cell 145, 312–321 (2011). This work elucidates mechanisms of thermal robustness for a bacterial signalling network.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kotte, O., Zaugg, J. B. & Heinemann, M. Bacterial adaptation through distributed sensing of metabolic fluxes. Mol. Syst. Biol. 6, 355 (2010).

    PubMed  PubMed Central  Google Scholar 

  49. Hart, Y. et al. Robust control of nitrogen assimilation by a bifunctional enzyme in E. coli. Mol. Cell 41, 117–127 (2011).

    CAS  PubMed  Google Scholar 

  50. Typas, A., Banzhaf, M., Gross, C. A. & Vollmer, W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat. Rev. Microbiol. 10, 123–136 (2012).

    CAS  Google Scholar 

  51. Ursell, T. S. et al. Rod-like bacterial shape is maintained by feedback between cell curvature and cytoskeletal localization. Proc. Natl Acad. Sci. USA 111, E1025–E1034 (2014).

    CAS  PubMed  Google Scholar 

  52. Maslov, S. & Sneppen, K. Specificity and stability in topology of protein networks. Science 296, 910–913 (2002).

    CAS  PubMed  Google Scholar 

  53. Li, G. W., Burkhardt, D., Gross, C. & Weissman, J. S. Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources. Cell 157, 624–635 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kovacs, K., Hurst, L. D. & Papp, B. Stochasticity in protein levels drives colinearity of gene order in metabolic operons of Escherichia coli. PLoS Biol. 7, e1000115 (2009).

    PubMed  PubMed Central  Google Scholar 

  55. Lovdok, L. et al. Role of translational coupling in robustness of bacterial chemotaxis pathway. PLoS Biol. 7, e1000171 (2009).

    PubMed  PubMed Central  Google Scholar 

  56. Milo, R. et al. Network motifs: simple building blocks of complex networks. Science 298, 824–827 (2002).

    CAS  PubMed  Google Scholar 

  57. Chen, S., Harrigan, P., Heineike, B., Stewart-Ornstein, J. & El-Samad, H. Building robust functionality in synthetic circuits using engineered feedback regulation. Curr. Opin. Biotechnol. 24, 790–796 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Wagner, A. The molecular origins of evolutionary innovations. Trends Genet. 27, 397–410 (2011).

    CAS  PubMed  Google Scholar 

  59. Wadhams, G. H. & Armitage, J. P. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell Biol. 5, 1024–1037 (2004).

    CAS  PubMed  Google Scholar 

  60. Sourjik, V. & Wingreen, N. S. Responding to chemical gradients: bacterial chemotaxis. Curr. Opin. Cell Biol. 24, 262–268 (2012).

    CAS  PubMed  Google Scholar 

  61. Minamino, T. & Imada, K. The bacterial flagellar motor and its structural diversity. Trends Microbiol. 23, 267–274 (2015).

    CAS  PubMed  Google Scholar 

  62. Sourjik, V. & Armitage, J. P. Spatial organization in bacterial chemotaxis. EMBO J. 29, 2724–2733 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Rajagopala, S. V., Hughes, K. T. & Uetz, P. Benchmarking yeast two-hybrid systems using the interactions of bacterial motility proteins. Proteomics 9, 5296–5302 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Morimoto, Y. V. et al. Assembly and stoichiometry of FliF and FlhA in Salmonella flagellar basal body. Mol. Microbiol. 91, 1214–1226 (2014).

    CAS  PubMed  Google Scholar 

  65. Sourjik, V. & Berg, H. C. Receptor sensitivity in bacterial chemotaxis. Proc. Natl Acad. Sci. USA 99, 123–127 (2002).

    CAS  PubMed  Google Scholar 

  66. Vaknin, A. & Berg, H. C. Physical responses of bacterial chemoreceptors. J. Mol. Biol. 366, 1416–1423 (2007).

    CAS  PubMed  Google Scholar 

  67. Vaknin, A. & Berg, H. C. Osmotic stress mechanically perturbs chemoreceptors in Escherichia coli. Proc. Natl Acad. Sci. USA 103, 592–596 (2006).

    CAS  PubMed  Google Scholar 

  68. Shimizu, T. S., Tu, Y. & Berg, H. C. A modular gradient-sensing network for chemotaxis in Escherichia coli revealed by responses to time-varying stimuli. Mol. Syst. Biol. 6, 382 (2010). This report demonstrates how FRET measurements of intracellular signal processing can be used to characterize the internal structure and dynamics of a network.

    PubMed  PubMed Central  Google Scholar 

  69. Hazelbauer, G. L. & Lai, W. C. Bacterial chemoreceptors: providing enhanced features to two-component signaling. Curr. Opin. Microbiol. 13, 124–132 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Schulmeister, S. et al. Protein exchange dynamics at chemoreceptor clusters in Escherichia coli. Proc. Natl Acad. Sci. USA 105, 6403–6408 (2008).

    CAS  PubMed  Google Scholar 

  71. Alon, U., Surette, M. G., Barkai, N. & Leibler, S. Robustness in bacterial chemotaxis. Nature 397, 168–171 (1999).

    CAS  PubMed  Google Scholar 

  72. Li, M. & Hazelbauer, G. L. Cellular stoichiometry of the components of the chemotaxis signaling complex. J. Bacteriol. 186, 3687–3694 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Emonet, T. & Cluzel, P. Relationship between cellular response and behavioral variability in bacterial chemotaxis. Proc. Natl Acad. Sci. USA 105, 3304–3309 (2008).

    CAS  PubMed  Google Scholar 

  74. Flores, M., Shimizu, T. S., ten Wolde, P. R. & Tostevin, F. Signaling noise enhances chemotactic drift of E. coli. Phys. Rev. Lett. 109, 148101 (2012).

    PubMed  Google Scholar 

  75. Marykwas, D. L., Schmidt, S. A. & Berg, H. C. Interacting components of the flagellar motor of Escherichia coli revealed by the two-hybrid system in yeast. J. Mol. Biol. 256, 564–576 (1996).

    CAS  PubMed  Google Scholar 

  76. Cohen-Ben-Lulu, G. N. et al. The bacterial flagellar switch complex is getting more complex. EMBO J. 27, 1134–1144 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Fang, X. & Gomelsky, M. A post-translational, c-di-GMP-dependent mechanism regulating flagellar motility. Mol. Microbiol. 76, 1295–1305 (2010).

    CAS  PubMed  Google Scholar 

  78. Paul, K., Nieto, V., Carlquist, W. C., Blair, D. F. & Harshey, R. M. The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a 'backstop brake' mechanism. Mol. Cell 38, 128–139 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Neumann, S., Grosse, K. & Sourjik, V. Chemotactic signaling via carbohydrate phosphotransferase systems in Escherichia coli. Proc. Natl Acad. Sci. USA 109, 12159–12164 (2012).

    CAS  PubMed  Google Scholar 

  80. Press, M. O. et al. Genome-scale co-evolutionary inference identifies functions and clients of bacterial Hsp90. PLoS Genet. 9, e1003631 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Salje, J., van den Ent, F., de Boer, P. & Löwe, J. Direct membrane binding by bacterial actin MreB. Mol. Cell 43, 478–487 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. van den Ent, F., Izore, T., Bharat, T. A., Johnson, C. M. & Löwe, J. Bacterial actin MreB forms antiparallel double filaments. eLife 3, e02634 (2014).

    PubMed  PubMed Central  Google Scholar 

  83. Strahl, H., Bürmann, F. & Hamoen, L. W. The actin homologue MreB organizes the bacterial cell membrane. Nat. Commun. 5, 3442 (2014).

    PubMed  PubMed Central  Google Scholar 

  84. Schirner, K. et al. Lipid-linked cell wall precursors regulate membrane association of bacterial actin MreB. Nat. Chem. Biol. 11, 38–45 (2015).

    CAS  PubMed  Google Scholar 

  85. Bendezú, F. O., Hale, C. A., Bernhardt, T. G. & de Boer, P. A. RodZ (YfgA) is required for proper assembly of the MreB actin cytoskeleton and cell shape in E. coli. EMBO J. 28, 193–204 (2009).

    PubMed  Google Scholar 

  86. van den Ent, F., Johnson, C. M., Persons, L., de Boer, P. & Löwe, J. Bacterial actin MreB assembles in complex with cell shape protein RodZ. EMBO J. 29, 1081–1090 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Szwedziak, P., Wang, Q., Bharat, T. A., Tsim, M. & Löwe, J. Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division. eLife 3, e04601 (2014).

    PubMed  PubMed Central  Google Scholar 

  88. Osawa, M. & Erickson, H. P. Liposome division by a simple bacterial division machinery. Proc. Natl Acad. Sci. USA 110, 11000–11004 (2013).

    CAS  PubMed  Google Scholar 

  89. Szwedziak, P., Wang, Q., Freund, S. M. & Löwe, J. FtsA forms actin-like protofilaments. EMBO J. 31, 2249–2260 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Loose, M. & Mitchison, T. J. The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns. Nat. Cell Biol. 16, 38–46 (2014).

    CAS  PubMed  Google Scholar 

  91. Mohammadi, T. et al. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J. 30, 1425–1432 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Sham, L. T. et al. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis. Science 345, 220–222 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Szwedziak, P. & Löwe, J. Do the divisome and elongasome share a common evolutionary past? Curr. Opin. Microbiol. 16, 745–751 (2013).

    CAS  PubMed  Google Scholar 

  94. Di Lallo, G., Fagioli, M., Barionovi, D., Ghelardini, P. & Paolozzi, L. Use of a two-hybrid assay to study the assembly of a complex multicomponent protein machinery: bacterial septosome differentiation. Microbiology 149, 3353–3359 (2003).

    CAS  PubMed  Google Scholar 

  95. Domínguez-Escobar, J. et al. Processive movement of MreB-associated cell wall biosynthetic complexes in bacteria. Science 333, 225–228 (2011).

    PubMed  Google Scholar 

  96. Garner, E. C. et al. Circumferential motions of the cell wall synthesis machinery drive cytoskeletal dynamics in B. subtilis. Science 333, 222–225 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. van Teeffelen, S. et al. The bacterial actin MreB rotates, and rotation depends on cell-wall assembly. Proc. Natl Acad. Sci. USA 108, 15822–15827 (2011).

    CAS  PubMed  Google Scholar 

  98. Bernard, C. S., Sadasivam, M., Shiomi, D. & Margolin, W. An altered FtsA can compensate for the loss of essential cell division protein FtsN in Escherichia coli. Mol. Microbiol. 64, 1289–1305 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Shiomi, D. et al. Mutations in cell elongation genes mreB, mrdA and mrdB suppress the shape defect of RodZ-deficient cells. Mol. Microbiol. 87, 1029–1044 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Fenton, A. K. & Gerdes, K. Direct interaction of FtsZ and MreB is required for septum synthesis and cell division in Escherichia coli. EMBO J. 32, 1953–1965 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. van der Ploeg, R. et al. Colocalization and interaction between elongasome and divisome during a preparative cell division phase in Escherichia coli. Mol. Microbiol. 87, 1074–1087 (2013).

    CAS  PubMed  Google Scholar 

  102. Aaron, M. et al. The tubulin homologue FtsZ contributes to cell elongation by guiding cell wall precursor synthesis in Caulobacter crescentus. Mol. Microbiol. 64, 938–952 (2007).

    CAS  PubMed  Google Scholar 

  103. Schaechter, M., Maaløe, O. & Kjeldgaard, N. O. Dependency on medium and temperature of cell size and chemical composition during balanced grown of Salmonella typhimurium. J. Gen. Microbiol. 19, 592–606 (1958).

    CAS  PubMed  Google Scholar 

  104. Jonas, K. To divide or not to divide: control of the bacterial cell cycle by environmental cues. Curr. Opin. Microbiol. 18, 54–60 (2014).

    CAS  PubMed  Google Scholar 

  105. Hill, N. S., Buske, P. J., Shi, Y. & Levin, P. A. A moonlighting enzyme links Escherichia coli cell size with central metabolism. PLoS Genet. 9, e1003663 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Beilharz, K. et al. Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP. Proc. Natl Acad. Sci. USA 109, E905–E913 (2012).

    CAS  PubMed  Google Scholar 

  107. Fleurie, A. et al. MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae. Nature 516, 259–262 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Abel, S. et al. Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks. Mol. Cell 43, 550–560 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Smith, S. C. et al. Cell cycle-dependent adaptor complex for ClpXP-mediated proteolysis directly integrates phosphorylation and second messenger signals. Proc. Natl Acad. Sci. USA 111, 14229–14234 (2014).

    CAS  PubMed  Google Scholar 

  110. Pinho, M. G., Kjos, M. & Veening, J. W. How to get (a)round: mechanisms controlling growth and division of coccoid bacteria. Nat. Rev. Microbiol. 11, 601–614 (2013).

    CAS  PubMed  Google Scholar 

  111. Goley, E. D. et al. Assembly of the Caulobacter cell division machine. Mol. Microbiol. 80, 1680–1698 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Kawai, Y., Asai, K. & Errington, J. Partial functional redundancy of MreB isoforms, MreB, Mbl and MreBH, in cell morphogenesis of Bacillus subtilis. Mol. Microbiol. 73, 719–731 (2009).

    CAS  PubMed  Google Scholar 

  113. Yang, D. C. et al. An ATP-binding cassette transporter-like complex governs cell-wall hydrolysis at the bacterial cytokinetic ring. Proc. Natl Acad. Sci. USA 108, E1052–E1060 (2011).

    PubMed  Google Scholar 

  114. Meisner, J. et al. FtsEX is required for CwlO peptidoglycan hydrolase activity during cell wall elongation in Bacillus subtilis. Mol. Microbiol. 89, 1069–1083 (2013). This study presents an example of network sub-module rewiring across evolution: an ABC transporter that energizes cell wall hyrdolysis is used by different cell cycle machineries in E. coli and B. subtilis.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Fields, S. & Song, O. A novel genetic system to detect protein–protein interactions. Nature 340, 245–246 (1989).

    CAS  PubMed  Google Scholar 

  116. Karimova, G., Pidoux, J., Ullmann, A. & Ladant, D. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc. Natl Acad. Sci. USA 95, 5752–5756 (1998).

    CAS  PubMed  Google Scholar 

  117. Yu, H. et al. High-quality binary protein interaction map of the yeast interactome network. Science 322, 104–110 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. von Mering, C. et al. Comparative assessment of large-scale data sets of protein–protein interactions. Nature 417, 399–403 (2002).

    CAS  PubMed  Google Scholar 

  119. Weimann, M. et al. A Y2H-seq approach defines the human protein methyltransferase interactome. Nat. Methods 10, 339–342 (2013).

    CAS  PubMed  Google Scholar 

  120. Boxem, M. et al. A protein domain-based interactome network for C. elegans early embryogenesis. Cell 134, 534–545 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Snider, J. et al. Mapping the functional yeast ABC transporter interactome. Nat. Chem. Biol. 9, 565–572 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Battesti, A. & Bouveret, E. The bacterial two-hybrid system based on adenylate cyclase reconstitution in Escherichia coli. Methods 58, 325–334 (2012).

    CAS  PubMed  Google Scholar 

  123. Beltrao, P., Cagney, G. & Krogan, N. J. Quantitative genetic interactions reveal biological modularity. Cell 141, 739–745 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Brochado, A. R. & Typas, A. High-throughput approaches to understanding gene function and mapping network architecture in bacteria. Curr. Opin. Microbiol. 16, 199–206 (2013). Together with reference 123, these reviews illustrate how high-throughput reverse genetics approaches can reveal new PPI links.

    CAS  PubMed  Google Scholar 

  125. Collins, S. R. et al. Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map. Nature 446, 806–810 (2007).

    CAS  PubMed  Google Scholar 

  126. Nichols, R. J. et al. Phenotypic landscape of a bacterial cell. Cell 144, 143–156 (2011).

    CAS  PubMed  Google Scholar 

  127. Roguev, A. et al. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast. Science 322, 405–410 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Typas, A. et al. Regulation of peptidoglycan synthesis by outer membrane proteins. Cell 143, 1097–1109 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Gavin, A. C., Maeda, K. & Kuhner, S. Recent advances in charting protein–protein interaction: mass spectrometry-based approaches. Curr. Opin. Biotechnol. 22, 42–49 (2011).

    CAS  PubMed  Google Scholar 

  130. Mellacheruvu, D. et al. The CRAPome: a contaminant repository for affinity purification–mass spectrometry data. Nat. Methods 10, 730–736 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Havugimana, P. C. et al. A census of human soluble protein complexes. Cell 150, 1068–1081 (2012). This report describes a novel biochemical approach, based on co-fractionation and proteomics, for identifying protein complexes in a cell.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Bui, K. H. et al. Integrated structural analysis of the human nuclear pore complex scaffold. Cell 155, 1233–1243 (2013).

    CAS  PubMed  Google Scholar 

  133. Sourjik, V., Vaknin, A., Shimizu, T. S. & Berg, H. C. In vivo measurement by FRET of pathway activity in bacterial chemotaxis. Methods Enzymol. 423, 365–391 (2007).

    CAS  PubMed  Google Scholar 

  134. Mascarenhas, J., Soppa, J., Strunnikov, A. V. & Graumann, P. L. Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein. EMBO J. 21, 3108–3118 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Matroule, J. Y., Lam, H., Burnette, D. T. & Jacobs-Wagner, C. Cytokinesis monitoring during development; rapid pole-to-pole shuttling of a signaling protein by localized kinase and phosphatase in Caulobacter. Cell 118, 579–590 (2004).

    CAS  PubMed  Google Scholar 

  136. Vaknin, A. & Berg, H. C. Single-cell FRET imaging of phosphatase activity in the Escherichia coli chemotaxis system. Proc. Natl Acad. Sci. USA 101, 17072–17077 (2004).

    CAS  PubMed  Google Scholar 

  137. Carillo, M. A., Bennet, M. & Faivre, D. Interaction of proteins associated with the magnetosome assembly in magnetotactic bacteria as revealed by two-hybrid two-photon excitation fluorescence lifetime imaging microscopy Forster resonance energy transfer. J. Phys. Chem. B 117, 14642–14648 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Maeder, C. I. et al. Spatial regulation of Fus3 MAP kinase activity through a reaction-diffusion mechanism in yeast pheromone signalling. Nat. Cell Biol. 9, 1319–1326 (2007).

    CAS  PubMed  Google Scholar 

  139. Kieser, K. J. & Rubin, E. J. How sisters grow apart: mycobacterial growth and division. Nat. Rev. Microbiol. 12, 550–562 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Brown, P. J. et al. Polar growth in the Alphaproteobacterial order Rhizobiales. Proc. Natl Acad. Sci. USA 109, 1697–1701 (2012).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to A.-R. Brochado and G. Kritikos for help with the figures, H. Li and A. Pollard for assisting with the literature search, and J. Selkrig and A. Pollard for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr 1, Heidelberg, 69117, Germany

    Athanasios Typas

  2. Max Planck Institute for Terrestrial Microbiology and LOEWE Center for Synthetic Microbiology (SYNMIKRO), Karl-von-Frisch Strasse 16, Marburg, 35043, Germany

    Victor Sourjik

Authors
  1. Athanasios Typas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victor Sourjik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Athanasios Typas or Victor Sourjik.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information S1 (figure)

Schematic of network interactions among the chemotaxis machinery and flagellar motor proteins in E. coli. (PDF 175 kb)

Supplementary information S2 (figure)

Schematic of the cell elongation and cell division networks in E. coli. (PDF 195 kb)

PowerPoint slides

Glossary

RNA degradosome

A ubiquitous multiprotein complex in bacteria that is involved in the processing of rRNA and degradation of mRNA. The complex includes RNaseE, polynucleotide phosphorylase, the RNA helicase RhlB, and enolase.

Allostery

The phenomenon by which the activity of a protein is regulated by the binding of another protein or ligand at a site other than the active site.

AAA+ family

(ATPase associated with diverse cellular activities family). A family of proteins that use ATP to induce conformational changes in their structure and thereby exert mechanical force on a substrate, which can result in substrate unfolding, degradation, translocation or movement.

Chemotaxis

The biased movement of an organism along a chemical gradient towards the source of an attractant or away from the source of a repellent.

Fluorescence anisotropy

The unequal emission of light by a fluorophore along different axes of polarization.

Horizontal gene transfer

The transfer of genes between organisms in a manner that differs from the vertical transfer of genes from parents to offspring via sexual or asexual reproduction.

Two-component signalling systems

Signal transduction systems that typically comprise two components, a sensory histidine kinase and a response regulator that is phosphorylated on an aspartyl residue and usually regulates transcription.

Siderophores

High-affinity iron chelators that are secreted by bacteria (and fungi) to scavenge soluble Fe3+

Carboxysomes

Intracellular protein-shelled microcompartments (∼100 nm in size) that occur in bacteria and contain enzymes involved in carbon fixation.

Gene expression noise

The variability in transcript levels in a population of isogenic cells or in the same cell over time.

Bet-hedging strategies

Strategies to diversify the phenotypes of genetically identical organisms, with the aim of increasing fitness and spreading risks in fluctuating environments.

Moonlighting enzyme

An enzyme that has additional functions to its canonical function.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Typas, A., Sourjik, V. Bacterial protein networks: properties and functions. Nat Rev Microbiol 13, 559–572 (2015). https://doi.org/10.1038/nrmicro3508

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro3508

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology