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  • Review Article
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Bacterial siderophores in community and host interactions

Nature Reviews Microbiology volume 18, pages 152–163 (2020)Cite this article

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Abstract

Iron is an essential trace element for most organisms. A common way for bacteria to acquire this nutrient is through the secretion of siderophores, which are secondary metabolites that scavenge iron from environmental stocks and deliver it to cells via specific receptors. While there has been tremendous interest in understanding the molecular basis of siderophore synthesis, uptake and regulation, questions about the ecological and evolutionary consequences of siderophore secretion have only recently received increasing attention. In this Review, we outline how eco-evolutionary questions can complement the mechanistic perspective and help to obtain a more integrated view of siderophores. In particular, we explain how secreted diffusible siderophores can affect other community members, leading to cooperative, exploitative and competitive interactions between individuals. These social interactions in turn can spur co-evolutionary arms races between strains and species, lead to ecological dependencies between them and potentially contribute to the formation of stable communities. In brief, this Review shows that siderophores are much more than just iron carriers: they are important mediators of interactions between members of microbial assemblies and the eukaryotic hosts they inhabit.

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Fig. 1: Representative examples of the four main chemical classes of siderophores.
Fig. 2: Comparison of siderophore-dependent and surface-dependent iron-uptake systems.
Fig. 3: Siderophores can synergistically increase iron uptake when bacteria live in groups.
Fig. 4: Siderophore-mediated social interactions.
Fig. 5: Siderophores induce eco-evolutionary dynamics in bacterial communities.
Fig. 6: Siderophores and their effects on hosts.

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References

  1. Andrews, S. C., Robinson, A. K. & Rodriguez-Quinones, F. Bacterial iron homeostasis. FEMS Microbiol. Rev. 27, 215–237 (2003).

    CAS  PubMed  Google Scholar 

  2. Boyd, P. W. & Ellwood, M. J. The biogeochemical cycle of iron in the ocean. Nat. Geosci. 3, 675–682 (2010).

    CAS  Google Scholar 

  3. Emerson, D., Roden, E. & Twining, B. S. The microbial ferrous wheel: iron cycling in terrestrial, freshwater, and marine environments. Front. Microbiol. 3, 383 (2012).

    PubMed  PubMed Central  Google Scholar 

  4. Guerinot, M. L. Microbial iron transport. Annu. Rev. Microbiol. 48, 743–772 (1994).

    CAS  PubMed  Google Scholar 

  5. Ratledge, C. & Dover, L. G. Iron metabolism in pathogenic bacteria. Annu. Rev. Microbiol. 54, 881–941 (2000).

    CAS  PubMed  Google Scholar 

  6. Miethke, M. & Marahiel, M. A. Siderophore-based iron acquisition and pathogen control. Microbiol. Mol. Biol. Rev. 71, 413–451 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cassat, J. E. & Skaar, E. P. Iron in infection and immunity. Cell Host Microbe 13, 509–519 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Frawley, E. R. & Fang, F. C. The ins and outs of bacterial iron metabolism. Mol. Microbiol. 93, 609–616 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Barber, M. F. & Elde, N. C. Buried treasure: evolutionary perspectives on microbial iron piracy. Trends Genet. 31, 627–636 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sheldon, J. R. & Heinrichs, D. E. Recent developments in understanding the iron acquisition strategies of gram positive pathogens. FEMS Microbiol. Rev. 39, 592–630 (2015).

    PubMed  Google Scholar 

  11. Boiteau, R. M. et al. Siderophore-based microbial adaptations to iron scarcity across the eastern Pacific Ocean. Proc. Natl Acad. Sci. USA. 113, 14237–14242 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Hider, R. C. & Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep. 27, 637–657 (2010). This is an extensive and comprehensive review on siderophore chemistry, biosynthesis and transport.

    CAS  PubMed  Google Scholar 

  13. Faraldo-Gómez, J. D. & Sansom, M. S. P. Acquisition of siderophores in gram-negative bacteria. Nat. Rev. Mol. Cell Biol. 4, 105–116 (2003).

    PubMed  Google Scholar 

  14. Wandersman, C. & Delepelaire, P. Bacterial iron sources: from siderophores to hemophores. Annu. Rev. Microbiol. 58, 611–647 (2004).

    CAS  PubMed  Google Scholar 

  15. West, S. A., Griffin, A. S., Gardner, A. & Diggle, S. P. Social evolution theory for microorganisms. Nat. Rev. Microbiol. 4, 597–607 (2006). This review offers a conceptual overview of social evolution theory as it applies to this review and microorganisms in general.

    CAS  PubMed  Google Scholar 

  16. Griffin, A., West, S. A. & Buckling, A. Cooperation and competition in pathogenic bacteria. Nature 430, 1024–1027 (2004). This study demonstrates for the first time that siderophores are a public good in Pseudomonas aeruginosa, and reveals conditions under which cheaters can spread in populations.

    CAS  PubMed  Google Scholar 

  17. Cordero, O. X., Ventouras, L.-A., DeLong, E. F. & Polz, M. F. Public good dynamics drive evolution of iron acquisition strategies in natural bacterioplankton populations. Proc. Natl Acad. Sci. USA. 109, 20059–20064 (2012). This study shows that public good interactions drive the evolution of siderophore-based iron-acquisition strategies in members of the family Vibrionaceae living on marine particles.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Kümmerli, R., Schiessl, K. T., Waldvogel, T., McNeill, K. & Ackermann, M. Habitat structure and the evolution of diffusible siderophores in bacteria. Ecol. Lett. 17, 1536–1544 (2014).

    PubMed  Google Scholar 

  19. Andersen, S. B., Marvig, R. L., Molin, S., Johansen, H. K. & Griffin, A. S. Long-term social dynamics drive loss of function in pathogenic bacteria. Proc. Natl Acad. Sci. USA. 112, 10756–10761 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Butaitė, E., Baumgartner, M., Wyder, S. & Kümmerli, R. Siderophore cheating and cheating resistance shape competition for iron in soil and freshwater Pseudomonas communities. Nat. Commun. 8, 414 (2017). This study shows that siderophore-mediated social interactions drive competitive dynamics in soil and freshwater communities of Pseudomonas bacteria.

    PubMed  PubMed Central  Google Scholar 

  21. Leinweber, A., Fredrik Inglis, R. & Kümmerli, R. Cheating fosters species co-existence in well-mixed bacterial communities. ISME J. 11, 1179–1188 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Andersen, S. B. et al. Privatisation rescues function following loss of cooperation. eLife 7, e38594 (2018). This study traces the evolutionary trajectory of siderophore production, exploitation and switch to alternative iron-uptake strategies in chronic lung infections of patients with cystic fibrosis.

    PubMed  PubMed Central  Google Scholar 

  23. Granato, E. T., Ziegenhain, C., Marvig, R. L. & Kummerli, R. Low spatial structure and selection against secreted virulence factors attenuates pathogenicity in Pseudomonas aeruginosa. ISME J. 12, 2907–2918 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Leventhal, G. E., Ackermann, M. & Schiessl, K. T. Why microbes secrete molecules to modify their environment: the case of iron-chelating siderophores. J. R. Soc. Interface 16, (2019). This theoretical study pins down the conditions under which siderophore secretion is favoured over surface-bound iron-uptake systems.

  25. Völker, C. & Wolf-Gladrow, D. A. Physical limits on iron uptake mediated by siderophores or surface reductases. Mar. Chem. 65, 227–244 (1999).

    Google Scholar 

  26. Niehus, R., Picot, A., Oliveira, N. M., Mitri, S. & Foster, K. R. The evolution of siderophore production as a competitive trait. Evolution 71, 1443–1455 (2017). This theoretical study shows that siderophores can evolve as competitive agents against other bacteria lacking the cognate receptor required for siderophore uptake.

    CAS  PubMed  Google Scholar 

  27. Sandy, M. & Butler, A. Microbial iron acquisition: marine and terrestrial siderophores. Chem. Rev. 109, 4580–4595 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Kraemer, S. M., Duckworth, O. W., Harrington, J. M. & Schenkeveld, W. D. C. Metallophores and trace metal biogeochemistry. Aquat. Geochem. 21, 159–195 (2015).

    CAS  Google Scholar 

  29. Crosa, J. H. & Walsh, C. T. Genetics and assembly line enzymology of siderophore biosynthesis in bacteria. Microbiol. Mol. Biol. Rev. 66, 223–249 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Grünewald, J. & Marahiel, M. A. Chemoenzymatic and template-directed synthesis of bioactive macrocyclic peptides. Microbiol. Mol. Biol. Rev. 70, 121–146 (2006).

    PubMed  PubMed Central  Google Scholar 

  31. Donadio, S., Monciardini, P. & Sosio, M. Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics. Nat. Prod. Rep. 24, 1073–1109 (2007).

    CAS  PubMed  Google Scholar 

  32. Lamb, A. L. Breaking a pathogen’s iron will: inhibiting siderophore production as an antimicrobial strategy. Biochim. Biophys. Acta 1854, 1054–1070 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Carroll, C. S. & Moore, M. M. Ironing out siderophore biosynthesis: a review of non-ribosomal peptide synthetase (NRPS)-independent siderophore synthetases. Crit. Rev. Biochem. Mol. Biol. 53, 356–381 (2018).

    CAS  PubMed  Google Scholar 

  34. Krewulak, K. D. & Vogel, H. J. Structural biology of bacterial iron uptake. Biochim. Biophys. Acta 1778, 1781–1804 (2008).

    CAS  PubMed  Google Scholar 

  35. Schalk, I. J. & Guillon, L. Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. Amino Acids 44, 1267–1277 (2013).

    CAS  PubMed  Google Scholar 

  36. Ganne, G. et al. Iron release from the siderophore pyoverdine in Pseudomonas aeruginosa involves three new actors: FpvC, FpvG, and FpvH. ACS Chem. Biol. 12, 1056–1065 (2017).

    CAS  PubMed  Google Scholar 

  37. Imperi, F., Tiburzi, F. & Visca, P. Molecular basis of pyoverdine siderophore recycling in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 106, 20440–20445 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Jones, C. M. et al. Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling. Proc. Natl Acad. Sci. USA 111, 1945–1950 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Lin, H., Fischbach, M. A., Liu, D. R. & Walsh, C. T. In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes. J. Am. Chem. Soc. 127, 11075–11084 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Neumann, W., Sassone-Corsi, M., Raffatellu, M. & Nolan, E. M. Esterase-catalyzed siderophore hydrolysis activates an enterobactin-ciprofloxacin conjugate and confers targeted antibacterial activity. J. Am. Chem. Soc. 140, 5193–5201 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Escolar, L., Pérez-Martín, J. & de Lorenzo, V. Opening the iron box: transcriptional metalloregulation by the fur protein. J. Bacteriol. 181, 6223–6229 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Troxell, B. & Hassan, H. M. Transcriptional regulation by ferric uptake regulator (Fur) in pathogenic bacteria. Front. Cell. Infect. Microbiol. 3, 59 (2013).

    PubMed  PubMed Central  Google Scholar 

  43. Leoni, L., Orsi, N., de Lorenzo, V. & Visca, P. Functional analysis of PvdS, an iron starvation sigma factor of Pseudomonas aeruginosa. J. Bacteriol. 182, 1481–1491 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Lamont, I. L., Beare, P., Ochsner, U., Vasil, A. I. & Vasil, M. L. Siderophore-mediated signaling regulates virulence factor production in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 99, 7072–7077 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Cornelis, P. Iron uptake and metabolism in pseudomonads. Appl. Microbiol. Biotechnol. 86, 1637–1645 (2010).

    CAS  PubMed  Google Scholar 

  46. Mathew, A., Eberl, L. & Carlier, A. L. A novel siderophore-independent strategy of iron uptake in the genus Burkholderia. Mol. Microbiol. 91, 805–820 (2014).

    CAS  PubMed  Google Scholar 

  47. Lau, C. K. Y., Krewulak, K. D. & Vogel, H. J. Bacterial ferrous iron transport: the Feo system. FEMS Microbiol. Rev. 40, 273–298 (2015).

    PubMed  Google Scholar 

  48. Vetter, Y. A., Deming, J. W., Jumars, P. A. & Krieger-Brockett, B. B. A predictive model of bacterial foraging by means of freely released extracellular enzymes. Microb. Ecol. 36, 75–92 (1998).

    CAS  PubMed  Google Scholar 

  49. Driscoll, W. W. & Pepper, J. W. Theory for the evolution of diffusible external goods. Evolution 64, 2682–2687 (2010).

    PubMed  Google Scholar 

  50. Allen, B., Gore, J. & Nowak, M. A. Spatial dilemmas of diffusible public goods. eLife 2, e01169 (2013).

    PubMed  PubMed Central  Google Scholar 

  51. Dobay, A., Bagheri, H. C., Messina, A., Kümmerli, R. & Rankin, D. J. Interaction effects of cell diffusion, cell density and public goods properties on the evolution of cooperation in digital microbes. J. Evol. Biol. 27, 1869–1877 (2014).

    CAS  PubMed  Google Scholar 

  52. Kümmerli, R., Griffin, A. S., West, S. A., Buckling, A. & Harrison, F. Viscous medium promotes cooperation in the pathogenic bacterium Pseudomonas aeruginosa. Proc. R. Soc. B 276, 3531–3538 (2009).

    PubMed  PubMed Central  Google Scholar 

  53. Xu, G., Martinez, J. S., Groves, J. T. & Butler, A. Membrane affinity of the amphiphilic marinobactin siderophores. J. Am. Chem. Soc. 124, 13408–13415 (2002).

    CAS  PubMed  Google Scholar 

  54. Martinez, J. L. et al. Structure and membrane affinity of a suite of amphiphilic siderophores produced by a marine bacterium. Proc. Natl Acad. Sci. USA 100, 3754–3759 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sidebottom, A. M., Johnson, A. R., Karty, J. A., Trader, D. J. & Carlson, E. E. Integrated metabolomics approach facilitates discovery of an unpredicted natural product suite from Streptomyces coelicolor M145. ACS Chem. Biol. 8, 2009–2016 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Claessen, D., Rozen, D. E., Kuipers, O. P., Søgaard-Andersen, L. & van Wezel, G. P. Bacterial solutions to multicellularity: a tale of biofilms, filaments and fruiting bodies. Nat. Rev. Microbiol. 12, 115–124 (2014).

    CAS  PubMed  Google Scholar 

  57. Flemming, H. C. et al. Biofilms: an emergent form of bacterial life. Nat. Rev. Microbiol. 14, 563–575 (2016).

    CAS  PubMed  Google Scholar 

  58. Flemming, H. C. & Wuertz, S. Bacteria and archaea on Earth and their abundance in biofilms. Nat. Rev. Microbiol. 17, 247–260 (2019).

    CAS  PubMed  Google Scholar 

  59. West, S. A., Diggle, S. P., Buckling, A., Gardner, A. & Griffin, A. S. The social lives of microbes. Annu. Rev. Ecol. Evol. Syst. 38, 53–77 (2007).

    Google Scholar 

  60. Ross-Gillespie, A., Gardner, A., Buckling, A., West, S. A. & Griffin, A. S. Density dependence and cooperation: theory and a test with bacteria. Evolution 63, 2315–2325 (2009).

    PubMed  Google Scholar 

  61. Buckling, A. et al. Siderophore-mediated cooperation and virulence in Pseudomonas aeruginosa. FEMS Microbiolol. Ecol. 62, 135–141 (2007).

    CAS  Google Scholar 

  62. West, S. A., Griffin, A. S. & Gardner, A. Social semantics: altruism, cooperation, mutualism, strong reciprocity and group selection. J. Evol. Biol. 20, 415–432 (2007).

    CAS  PubMed  Google Scholar 

  63. Sexton, D. J. & Schuster, M. Nutrient limitation determines the fitness of cheaters in bacterial siderophore cooperation. Nat. Commun. 8, 230 (2017).

    PubMed  PubMed Central  Google Scholar 

  64. Schiessl, K. T. et al. Individual- versus group-optimality in the production of secreted bacterial compounds. Evolution 73, 675–688 (2019).

    PubMed  PubMed Central  Google Scholar 

  65. Weigert, M. & Kümmerli, R. The physical boundaries of public goods cooperation between surface-attached bacterial cells. Proc. R. Soc. B 284, 20170631 (2017).

    PubMed  PubMed Central  Google Scholar 

  66. Harrison, F. Dynamic social behaviour in a bacterium: Pseudomonas aeruginosa partially compensates for siderophore loss to cheats. J. Evol. Biol. 26, 1370–1378 (2013).

    CAS  PubMed  Google Scholar 

  67. Julou, T. et al. Cell-cell contacts confine public goods diffusion inside Pseudomonas aeruginosa clonal microcolonies. Proc. Natl Acad. Sci. USA 110, 12577–12582 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Ross-Gillespie, A., Dumas, Z. & Kümmerli, R. Evolutionary dynamics of interlinked public goods traits: an experimental study of siderophore production in Pseudomonas aeruginosa. J. Evol. Biol. 28, 29–39 (2015).

    CAS  PubMed  Google Scholar 

  69. Sathe, S., Mathew, A., Agnoli, K., Eberl, L. & Kümmerli, R. Genetic architecture constrains exploitation of siderophore cooperation in Burkholderia cenocepacia. Evol. Lett. https://doi.org/10.1002/evl3.144 (2019).

    Article  Google Scholar 

  70. Scholz, R. L. & Greenberg, E. P. Sociality in Escherichia coli: enterochelin is a private good at low cell density and can be shared at high cell density. J. Bacteriol. 197, 2122–2128 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Kümmerli, R. & Brown, S. P. Molecular and regulatory properties of a public good shape the evolution of cooperation. Proc. Natl Acad. Sci. USA 107, 18921–18926 (2010).

    PubMed  PubMed Central  Google Scholar 

  72. MacLean, R. C. The tragedy of the commons in microbial populations: insights from theoretical, comparative and experimental studies. Heredity 100, 233–239 (2008).

    CAS  PubMed  Google Scholar 

  73. Ghoul, M., Griffin, A. S. & West, S. A. Toward and evolutionary definition of cheating. Evolution 68, 318–331 (2014).

    PubMed  Google Scholar 

  74. Hardin, G. The tragedy of the commons. Science 162, 1243–1248 (1968).

    CAS  PubMed  Google Scholar 

  75. Rankin, D. J., Bargum, K. & Kokko, H. The tragedy of the commons in evolutionary biology. Trends Ecol. Evol. 22, 643–651 (2007).

    PubMed  Google Scholar 

  76. Özkaya, Ö., Xavier, K. B., Dionisio, F. & Balbontin, R. Maintenance of microbial cooperation mediated by public goods in single and multiple traits scenarios. J. Bacteriol. 199, e00297-00217 (2017).

    PubMed Central  Google Scholar 

  77. Jiricny, N. et al. Fitness correlates with the extent of cheating in a bacterium. J. Evol. Biol. 23, 738–747 (2010).

    CAS  PubMed  Google Scholar 

  78. Dumas, Z. & Kümmerli, R. Cost of cooperation rules selection for cheats in bacterial metapopulations. J. Evol. Biol. 25, 473–484 (2012).

    CAS  PubMed  Google Scholar 

  79. Tekwa, E. W., Nguyen, D., Loreau, M. & Gonzalez, A. Defector clustering is linked to cooperation in a pathogenic bacterium. Proc. R. Soc. B 284, 20172001 (2017).

    PubMed  PubMed Central  Google Scholar 

  80. Becker, F., Wienand, K., Lechner, M., Frey, E. & Jung, H. Interactions mediated by a public good transiently increase cooperativity in growing Pseudomonas putida metapopulations. Sci. Rep. 8, 4093 (2018).

    PubMed  PubMed Central  Google Scholar 

  81. Özkaya, Ö., Balbontin, R., Gordo, I. & Xavier, K. B. Cheating on cheaters stabilizes cooperation in Pseudomonas aeruginosa. Curr. Biol. 28, 2070–2080 (2018).

    PubMed  Google Scholar 

  82. Kümmerli, R. et al. Co-evolutionary dynamics between public good producers and cheats in the bacterium Pseudomonas aeruginosa. J. Evol. Biol. 28, 2264–2274 (2015).

    PubMed  Google Scholar 

  83. Vasse, M., Torres-Barcelo, C. & Hochberg, M. E. Phage selection for bacterial cheats leads to population decline. Proc. R. Soc. B 282, 20152207 (2015).

    PubMed  PubMed Central  Google Scholar 

  84. Vasse, M. et al. Antibiotic stress selects against cooperation in the pathogenic bacterium Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 114, 546–551 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Bruce, J. B., West, S. A. & Griffin, A. S. Functional amyloids promote retention of public goods in bacteria. Proc. R. Soc. B 286, 20190709 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Kümmerli, R., Jiricny, N., Clarke, L. S., West, S. A. & Griffin, A. S. Phenotypic plasticity of a cooperative behaviour in bacteria. J. Evol. Biol. 22, 589–598 (2009).

    PubMed  Google Scholar 

  87. Ghoul, M. et al. Pyoverdin cheats fail to invade bacterial populations in stationary phase. J. Evol. Biol. 29, 1728–1736 (2016).

    CAS  PubMed  Google Scholar 

  88. Ross-Gillespie, A., Gardner, A., West, S. A. & Griffin, A. S. Frequency dependence and cooperation: theory and a test with bacteria. Am. Nat. 170, 331–342 (2007).

    PubMed  Google Scholar 

  89. Morris, J. J. Black Queen evolution: the role of leakiness in structuring microbial communities. Trends Genet. 31, 475–482 (2015). This review explains how secreted and leaky metabolites can spur the evolution of trait loss and dependencies in microbial communities.

    CAS  PubMed  Google Scholar 

  90. Bruce, J. B., Cooper, G. A., Chabas, H., West, S. A. & Griffin, A. S. Cheating and resistance to cheating in natural populations of the bacterium Pseudomonas fluorescens. Evolution 71, 2484–2495 (2017).

    CAS  PubMed  Google Scholar 

  91. De Vos, D. et al. Study of pyoverdin type and production by Pseudomonas aeruginosa isolated from cystic fibrosis patients: prevalence of type II pyoverdine isolates and accumulation of pyoverdine-negative mutations. Arch. Microbiol. 175, 384–388 (2001).

    PubMed  Google Scholar 

  92. Jiricny, N. et al. Loss of social behaviours in populations of Pseudomonas aeruginosa infecting lungs of patients with cystic fibrosis. PLOS ONE 9, e83124 (2014).

    PubMed  PubMed Central  Google Scholar 

  93. Lujan, A. M., Pedro, G. & Buckling, A. Siderophore cooperation of the bacterium Pseudomonas fluorescens in soil. Biol. Lett. 11, 20140934 (2015).

    PubMed  PubMed Central  Google Scholar 

  94. Zhang, X. X. & Rainey, P. B. Exploring the sociobiology of pyoverdin-producing Pseudomonas. Evolution 67, 3161–3174 (2013).

    PubMed  Google Scholar 

  95. Butaitė, E., Kramer, J., Wyder, S. & Kümmerli, R. Environmental determinants of pyoverdine production, exploitation and competition in natural Pseudomonas communities. Environ. Microbiol. 20, 3629–3642 (2018).

    PubMed  PubMed Central  Google Scholar 

  96. Schiessl, K. T., Janssen, E. M. L., Kraemer, S. M., McNeill, K. & Ackermann, M. Magnitude and mechanism of siderophore-mediated competition at low iron solubility in the Pseudomonas aeruginosa pyochelin system. Front. Microbiol. 8, 1964 (2017).

    PubMed  PubMed Central  Google Scholar 

  97. Inglis, R. F., Biernaskie, J. M., Gardner, A. & Kümmerli, R. Presence of a loner strain maintains cooperation and diversity in well-mixed bacterial communities. Proc. R. Soc. B 283, 20152682 (2016).

    PubMed  PubMed Central  Google Scholar 

  98. Harrison, F., Paul, J., Massey, R. C. & Buckling, A. Interspecific competition and siderophore-mediated cooperation in Pseudomonas aeruginosa. ISME J. 2, 49–55 (2008). This study shows that siderophores can act as competitive agents in interspecific competition.

    PubMed  Google Scholar 

  99. Leinweber, A., Weigert, M. & Kummerli, R. The bacterium Pseudomonas aeruginosa senses and gradually responds to interspecific competition for iron. Evolution 72, 1515–1528 (2018).

    CAS  PubMed Central  Google Scholar 

  100. Dawkins, R. & Krebs, J. R. Arms races between and within species. Proc. R. Soc. B 205, 489–511 (1979).

    CAS  Google Scholar 

  101. Lee, W., van Baalen, M. & Jansen, V. A. A. Siderophore production and the evolution of investment in a public good: An adaptive dynamics approach to kin selection. J. Theor. Biol. 388, 61–71 (2016).

    CAS  PubMed  Google Scholar 

  102. O’Brien, S., Lujan, A. M., Paterson, S., Cant, M. A. & Buckling, A. Adaptation to public goods cheats in Pseudomonas aeruginosa. Proc. R. Soc. B 284, 20171089 (2017).

    PubMed  PubMed Central  Google Scholar 

  103. Smith, E. E., Sims, E. H., Spencer, D. H., Kaul, R. & Olson, M. V. Evidence for diversifying selection at the pyoverdine locus of Pseudomonas aeruginosa. J. Bacteriol. 187, 2138–2147 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Meyer, J. M. et al. Siderotyping of fluorescent Pseudomonas: molecular mass determination by mass spectrometry as a powerful pyoverdine siderotyping method. Biometals 21, 259–271 (2008).

    CAS  PubMed  Google Scholar 

  105. Lee, W., van Baalen, M. & Jansen, V. A. A. An evolutionary mechanism for diversity in siderophore producing bacteria. Ecol. Lett. 15, 119–125 (2012). This theoretical study shows how competitive interactions between cheaters and cooperators can drive the diversification of siderophores.

    PubMed  Google Scholar 

  106. Sexton, D. J., Glover, R. C., Loper, J. E. & Schuster, M. Pseudomonas protegens Pf-5 favours self-produced siderophore over free-loading in interspecies competition for iron. Environ. Microbiol. 19, 3514–3525 (2017).

    CAS  PubMed  Google Scholar 

  107. Stilwell, P., Lowe, C. & Buckling, A. The effect of cheats on siderophore diversity in Pseudomonas aeruginosa. J. Evol. Biol. 31, 1330–1339 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Jurkevitch, E., Hadar, Y. & Chen, Y. Differential siderophore utilization and iron uptake by soil and rhizosphere bacteria. Appl. Environ. Microbiol. 58, 119–124 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Champomier-Vergès, M. C., Stintzi, A. & Meyer, J. M. Acquisition of iron by the non-siderophore-producing Pseudomonas fragi. Microbiology 142, 1191–1199 (1996).

    PubMed  Google Scholar 

  110. Llamas, M. A. et al. The heterologous siderophores ferrioxamine B and ferrichrome activate signaling pathways in Pseudomonas aeruginosa. J. Bacteriol. 188, 1882–1891 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Lemos, M. L., Balado, M. & Osorio, C. R. Anguibactin- versus vanchrobactin-mediated iron uptake in Vibrio anguillarum: evolution and ecology of a fish pathogen. Environ. Microbiol. Rep. 2, 19–26 (2010).

    CAS  PubMed  Google Scholar 

  112. Dumas, Z., Ross-Gillespie, A. & Kümmerli, R. Switching between apparently redundant iron-uptake mechanisms benefits bacteria in changeable environments. Proc. R. Soc. B 280, 20131055 (2013).

    PubMed  PubMed Central  Google Scholar 

  113. Tyrrell, J. et al. Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia. BioMetals 28, 367–380 (2015).

    CAS  PubMed  Google Scholar 

  114. Estrela, S., Morris, J. J. & Kerr, B. Private benefits and metabolic conflicts shape the emergence of microbial interdependencies. Environ. Microbiol. 18, 1415–1427 (2016).

    PubMed  Google Scholar 

  115. D’Onofrio, A. et al. Siderophores from neighboring organisms promote the growth of uncultured bacteria. Chem. Biol. 17, 254–264 (2010). This study shows that unculturable marine bacteria become culturable on the supplementation of exogenous siderophores, demonstrating the existence of complete ecological dependencies.

    PubMed  PubMed Central  Google Scholar 

  116. Kerr, B., Riley, M. A., Feldman, M. W. & Bohannan, B. J. M. Local dispersal promotes biodiversity in a real-life game of rock-paper-scissors. Nature 418, 171–174 (2002). This study shows (theoretically and empirically) that non-transitive rock–paper–scissor dynamics can maintain species diversity in bacterial communities.

    CAS  PubMed  Google Scholar 

  117. Allesina, S. & Levine, J. M. A competitive network theory of species diversity. Proc. Natl Acad. Sci. USA 108, 5638–5642 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Kelsic, E. D., Zhao, J., Vetsigian, K. & Kishony, R. Counteraction of antibiotic production and degradation stabilizes microbial communities. Nature 521, 516–519 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Diggle, S. P., Griffin, A. S., Campell, G. S. & West, S. A. Cooperation and conflict in quorum-sensing bacterial populations. Nature 450, 411–414 (2007).

    CAS  PubMed  Google Scholar 

  120. Xavier, J. B., Kim, W. & Foster, K. R. A molecular mechanism that stabilizes cooperative secretions in Pseudomonas aeruginosa. Mol. Microbiol. 79, 166–179 (2011).

    CAS  PubMed  Google Scholar 

  121. Crespi, B. J. The evolution of social behavior in microorganisms. Trends Ecol. Evol. 16, 178–183 (2001).

    PubMed  Google Scholar 

  122. Brown, S. P. & Taylor, P. D. Joint evolution of multiple social traits: a kin selection analysis. Proc. R. Soc. B 277, 415–422 (2010).

    PubMed  Google Scholar 

  123. Driscoll, W. W., Pepper, J. W., Pierson, L. S. & Pierson, E. A. Spontaneous Gac mutants of Pseudomonas biological control strains: cheaters or mutualists. Appl. Environ. Microbiol. 77, 7227–7235 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Morris, J. J., Lenski, R. E. & Zinser, E. R. The black queen hypothesis: evolution of dependencies through adaptive gene loss. mBio 3, e00036–00012 (2012).

    PubMed  PubMed Central  Google Scholar 

  125. Shou, W., Ram, S. & Vilar, J. M. Synthetic cooperation in engineered yeast populations. Proc. Natl Acad. Sci. USA 104, 1877–1882 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Harcombe, W. R. Novel cooperation experimentally evolved between species. Evolution 64, 2166–2172 (2010).

    PubMed  Google Scholar 

  127. Pande, S. & Kost, C. Bacterial unculturability and the formation of intercellular metabolic networks. Trends Microbiol. 25, 349–361 (2017).

    CAS  PubMed  Google Scholar 

  128. Amin, S. A. et al. Photolysis of iron-siderophore chelates promotes bacterial-algal mutualism. Proc. Natl Acad. Sci. USA. 106, 17071–17076 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Oliveira, N. M., Niehus, R. & Foster, K. R. Evolutionary limits to cooperation in microbial communities. Proc. Natl Acad. Sci. USA. 111, 17941–17946 (2014). This conceptual study explains why the evolution of cooperative mutual exchange of secreted compounds is constrained in bacterial communities.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Foster, K. R. & Bell, T. Competition, not cooperation, dominates interactions among culturable microbial species. Curr. Biol. 22, 1845–1850 (2012).

    CAS  PubMed  Google Scholar 

  131. Koskella, B., Hall, L. J. & Metcalf, C. J. E. The microbiome beyond the horizon of ecological and evolutionary theory. Nat. Ecol. Evol. 1, 1606–1615 (2017).

    PubMed  Google Scholar 

  132. Loper, J. E. & Buyer, J. S. Siderophores in microbial interactions on plant surfaces. Mol. Plant Microbe Interact. 4, 5–13 (1991).

    CAS  Google Scholar 

  133. Raaijmakers, J. M. et al. Utilisation of heterologous siderophores and rhizosphere competence of fluorescent Pseudomonas spp. Can. J. Microbiol. 41, 126–135 (1995).

    CAS  Google Scholar 

  134. Fierer, N. Embracing the unknown: disentangling the complexities of the soil microbiome. Nat. Rev. Microbiol. 15, 579–590 (2017).

    CAS  PubMed  Google Scholar 

  135. Kupferschmied, P., Maurhofer, M. & Keel, C. Promise for plant pest control: root-associated pseudomonads with insecticidal activities. Front. Plant. Sci. 4, 287–287 (2013).

    PubMed  PubMed Central  Google Scholar 

  136. Pieterse, C. M. et al. Induced systemic resistance by beneficial microbes. Annu. Rev. Phytopathol. 52, 347–375 (2014).

    CAS  PubMed  Google Scholar 

  137. Deriu, E. et al. Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron. Cell Host Microbe 14, 26–37 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Sassone-Corsi, M. et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature 540, 280–283 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Granato, E. T., Harrison, F., Kümmerli, R. & Ross-Gillespie, A. Do bacterial “virulence factors” always increase virulence? A meta-analysis of pyoverdine production in Pseudomonas aeruginosa as a test case. Front. Microbiol. 7, 1952 (2016).

    PubMed  PubMed Central  Google Scholar 

  140. Harrison, F., Browning, L. E., Vos, M. & Buckling, A. Cooperation and virulence in acute Pseudomonas aeruginosa infections. BMC Biol. 4, 21 (2006).

    PubMed  PubMed Central  Google Scholar 

  141. Marvig, R. L. et al. Within-host evolution of Pseudomonas aeruginosa reveals adaptation. mBio 5, 1–8 (2014).

    Google Scholar 

  142. Harrison, F. Microbial ecology of the cystic fibrosis lung. Microbiology 153, 917–923 (2007).

    CAS  PubMed  Google Scholar 

  143. Callaghan, M. & McClean, S. Bacterial host interactions in cystic fibrosis. Curr. Opin. Microbiol. 15, 71–77 (2012).

    PubMed  Google Scholar 

  144. Cutting, G. R. Cystic fibrosis genetics: from molecular understanding to clinical application. Nat. Rev. Genet. 16, 45–56 (2015).

    CAS  PubMed  Google Scholar 

  145. Cornelis, P. & Dingemans, J. Pseudomonas aeruginosa adapts its iron uptake strategies in function of the type of infections. Front. Cell. Infect. Microbiol. 3, 75 (2013).

    PubMed  PubMed Central  Google Scholar 

  146. Ford, S. A., Kao, D., Williams, D. & King, K. C. Microbe-mediated host defence drives the evolution of reduced pathogen virulence. Nat. Commun. 7, 13430 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Tinbergen, N. On aims and methods of ethology. Z. Tierpsychol. 20, 410–433 (1963).

    Google Scholar 

  148. Sessions, A. L., Doughty, D. M., Welander, P. V., Summons, R. E. & Newman, D. K. The continuing puzzle of the great oxidation event. Curr. Biol. 19, R567–R574 (2009).

    CAS  PubMed  Google Scholar 

  149. Braud, A., Hoegy, F., Jezequel, K., Lebeau, T. & Schalk, I. J. New insights into the metal specificity of the Pseudomonas aeruginosa pyoverdine–iron uptake pathway. Environ. Microbiol. 11, 1079–1091 (2009).

    CAS  PubMed  Google Scholar 

  150. Braud, A., Geoffroy, V., Hoegy, F., Mislin, G. L. A. & Schalk, I. J. Presence of the siderophores pyoverdine and pyochelin in the extracellular medium reduces toxic metal accumulation in Pseudomonas aeruginosa and increases bacterial metal tolerance. Environ. Microbiol. Rep. 2, 419–425 (2010).

    CAS  PubMed  Google Scholar 

  151. Bobrov, A. G. et al. The Yersinia pestis siderophore, yersiniabactin, and the ZnuABC system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice. Mol. Microbiol. 93, 759–775 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Perry, R. D., Bobrov, A. G. & Fetherston, J. D. The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis. Metallomics 7, 965–978 (2015).

    CAS  PubMed  Google Scholar 

  153. Koh, E. I. & Henderson, J. P. Microbial copper-binding siderophores at the host-pathogen interface. J. Biol. Chem. 290, 18967–18974 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Robinson, A. E., Lowe, J. E., Koh, E. I. & Henderson, J. P. Uropathogenic enterobacteria use the yersiniabactin metallophore system to acquire nickel. J. Biol. Chem. 293, 14953–14961 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Giller, K. E., Witter, E. & McGrath, S. P. Toxicity of heavy metals to microorganisms and microbial processes in agricultural soils: a review. Soil Biol. Biochem. 30, 1389–1414 (1998).

    CAS  Google Scholar 

  156. Schalk, I. J., Hannauer, M. & Braud, A. New roles for bacterial siderophores in metal transport and tolerance. Environ. Microbiol. 13, 2844–2854 (2011).

    CAS  PubMed  Google Scholar 

  157. Hesse, E. et al. Ecological selection of siderophore-producing microbial taxa in response to heavy metal contamination. Ecol. Lett. 21, 117–127 (2018).

    PubMed  Google Scholar 

  158. O’Brien, S., Hodgson, D. J. & Buckling, A. Social evolution of toxic metal bioremediation in Pseudomonas aeruginosa. Proc. R. Soc. B 281, 20140858 (2014).

    PubMed  PubMed Central  Google Scholar 

  159. Guan, L. L., Kanoh, K. & Kamino, K. Effect of exogenous siderophores on iron uptake activity of marine bacteria under iron-limited conditions. Appl. Environ. Microbiol. 67, 1710–1717 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Grandchamp, G. M., Caro, L. & Shank, E. A. Pirated siderophores promote sporulation in Bacillus subtilis. Appl. Environ. Microbiol. 83, e03293-16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Burke, R. M., Upton, M. E. & McLoughlin, A. J. Influence of pigment production on resistance to ultraviolet irradiation in Pseudomonas aeruginosa ATCC 10145. Ir. J. Food Sci. Technol. 14, 51–60 (1990).

    Google Scholar 

  162. Achard, M. E. et al. An antioxidant role for catecholate siderophores in. Salmonella. Biochem. J. 454, 543–549 (2013).

    CAS  PubMed  Google Scholar 

  163. Adler, C. et al. The alternative role of enterobactin as an oxidative stress protector allows Escherichia coli colony development. PLOS ONE 9, e84734 (2014).

    PubMed  PubMed Central  Google Scholar 

  164. Jin, Z. et al. Conditional privatization of a public siderophore enables Pseudomonas aeruginosa to resist cheater invasion. Nat. Commun. 9, 1383 (2018).

    PubMed  PubMed Central  Google Scholar 

  165. Braun, V., Pramanik, A., Gwinner, T., Köberle, M. & Bohn, E. Sidermycins: tools and antibiotics. Biometals 22, 3–13 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was funded by the European Research Council under grant agreement no. 681295 and the Swiss National Science Foundation under grant no. 31003A_182499 (both to R. K.), the German Science Foundation under grant no. KR 5017/2-1 (to J. K.) and a University Research Priority Program (Evolution in Action) grant (to Ö. Ö.).

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    Jos Kramer, Özhan Özkaya & Rolf Kümmerli

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Glossary

Siderophores

Secondary metabolites with high affinity and specificity for iron that function as organic ligands, serve the purpose of iron acquisition and are regulated in response to the producer’s need for iron.

Biofilms

Aggregates of microorganisms that are embedded within a self-produced matrix of extracellular polymeric substances and that adhere to each other and/or a surface.

Cooperation

A social behaviour which provides a benefit to another individual and which has evolved and/or is currently maintained (at least partly) because of its beneficial effect on the recipient.

Pseudomonas aeruginosa

A metabolically versatile, ubiquitous, rod-shaped, Gram-negative bacterium that can opportunistically infect plants, animals and humans and is known for its high intrinsic resistance to antibiotics.

Public goods

Costly resources that benefit not only the producer but also other members of the population or local community.

Tragedy of the commons

A situation in which cooperation would be beneficial in the long term but breaks down because individuals selfishly pursue their own short-term interests.

Negative frequency-dependent selection

An evolutionary process by which the relative fitness of a phenotype is high when it occurs at low frequency in the population but decreases as it becomes more common relative to other phenotypes.

Cheating

Exploitation of a cooperative behaviour by an individual that does not cooperate (or cooperates less than its fair share), whereby the cheating individual reaps the benefits of cooperation at the expense of the cooperating individual.

Competition

A situation that arises when two or more individuals of the same species or different species strive for the same limited resource, resulting in immediate costs for all individuals involved.

Horizontal gene transfer

The transfer of genetic material from one individual to another individual (of the same species or a different species) that does not involve the vertical transmission of DNA typical of cell division and reproduction.

Co-evolutionary arms races

Evolutionary tug of war between competing strains or species, whereby adaptations in one party select for counteradaptations in the other party.

Non-transitive population dynamics

Population dynamics arising from non-hierarchical circular competitive relationships between species, in which each species is both superior and inferior to different community members, with no overall winner existing in the population.

Metallophores

Secondary metabolites with high affinity and specificity for a given metal. They function as an organic ligand, serve the purpose of acquiring the metal in question and are regulated in response to metal limitation.

Division of labour

The division of a task that occurs when cooperating individuals specialize to carry out specific subtasks.

Cross-feeding

A nutritional interdependence between different strains or species in which each species feeds on the metabolic products released by the other species.

Virulence

The damage caused to the host by a parasite or pathogen, measured as the decrease in host fitness.

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Kramer, J., Özkaya, Ö. & Kümmerli, R. Bacterial siderophores in community and host interactions. Nat Rev Microbiol 18, 152–163 (2020). https://doi.org/10.1038/s41579-019-0284-4

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