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Exploring the host range for genetic transfer of magnetic organelle biosynthesis

Nature Nanotechnology (2023)Cite this article

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Abstract

Magnetosomes produced by magnetotactic bacteria have great potential for application in biotechnology and medicine due to their unique physicochemical properties and high biocompatibility. Attempts to transfer the genes for magnetosome biosynthesis into non-magnetic organisms have had mixed results. Here we report on a systematic study to identify key components needed for magnetosome biosynthesis after gene transfer. We transfer magnetosome genes to 25 proteobacterial hosts, generating seven new magnetosome-producing strains. We characterize the recombinant magnetosomes produced by these strains and demonstrate that denitrification and anaerobic photosynthesis are linked to the ability to synthesize magnetosomes upon the gene transfer. In addition, we show that the number of magnetosomes synthesized by a foreign host negatively correlates with the guanine–cytosine content difference between the host and the gene donor. Our findings have profound implications for the generation of magnetized living cells and the potential for transgenic biogenic magnetic nanoparticle production.

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Fig. 1: Experimental strategy used to survey bacterial hosts for heterologous magnetosome production.
Fig. 2: Overview of the magnetosome-producing hosts.
Fig. 3: Crystallographic analysis of the magnetosomes produced by C. sphaeroides MAG and Rhodopseudomonas pseudopalustris MAG.
Fig. 4: Crystallographic analysis of the magnetosomes produced by Rhodomicrobium vannielii MAG.
Fig. 5: Impact of pH on the magnetosome biosynthesis in Rhodoblastus acidophilus MAG.
Fig. 6: Genome–genome comparisons of M+ and M– strains.

Data availability

The dataset used for the comparative analysis of the orthologues across the genomes is deposited to the following repository together with the tidy data and the code for the analysis: https://github.com/MarDZiuba/pangenomemtx_to_Venn. Sequencing reads originating from this study were deposited to NCBI GenBank under the BioProject number PRJNA923495. Source data are provided with this paper.

Code availability

The script used to compare the orthologues and visualize the result is available at https://github.com/MarDZiuba/pangenomemtx_to_Venn.git. The script used to parse the magnetosome size measurements and generate the violin plots can be accessed at https://github.com/MarDZiuba/magsizeplot.git.

References

  1. Choi, J., Hwang, J., Kim, J. Y. & Choi, H. Recent progress in magnetically actuated microrobots for targeted delivery of therapeutic agents. Adv. Healthc. Mater. 10, 2001596 (2021).

    Article  CAS  Google Scholar 

  2. Schmidt, C. K., Medina-Sánchez, M., Edmondson, R. J. & Schmidt, O. G. Engineering microrobots for targeted cancer therapies from a medical perspective. Nat. Commun. 11, 5618 (2020).

    Article  CAS  Google Scholar 

  3. Aubry, M. et al. Engineering E. coli for magnetic control and the spatial localization of functions. ACS Synth. Biol. 9, 3030–3041 (2020).

    Article  CAS  Google Scholar 

  4. Cho, I. H. & Ku, S. Current technical approaches for the early detection of foodborne pathogens: challenges and opportunities. Int. J. Mol. Sci. 18, 2078 (2017).

    Article  Google Scholar 

  5. Taukulis, R. et al. Magnetic iron oxide nanoparticles as MRI contrast agents – a comprehensive physical and theoretical study. Magnetohydrodynamics 51, 721–748 (2015).

    Article  Google Scholar 

  6. Huang, J., Zhong, X., Wang, L., Yang, L. & Mao, H. Improving the magnetic resonance imaging contrast and detection methods with engineered magnetic nanoparticles. Theranostics 2, 86–102 (2012).

    Article  Google Scholar 

  7. Nishida, K. & Silver, P. A. Induction of biogenic magnetization and redox control by a component of the target of rapamycin complex 1 signaling pathway. PLoS Biol. 10, e1001269 (2012).

    Article  CAS  Google Scholar 

  8. Nimpf, S. & Keays, D. A. Is magnetogenetics the new optogenetics? EMBO J. 36, 1643–1646 (2017).

    Article  CAS  Google Scholar 

  9. Pekarsky, A. & Spadiut, O. Intrinsically magnetic cells: a review on their natural occurrence and synthetic generation. Front. Bioeng. Biotechnol. 8, 573183 (2020).

    Article  Google Scholar 

  10. Del Sol-Fernández, S. et al. Magnetogenetics: remote activation of cellular functions triggered by magnetic switches. Nanoscale 14, 2091–2118 (2022).

    Article  Google Scholar 

  11. Vargas, G. et al. Applications of magnetotactic bacteria, magnetosomes and magnetosome crystals in biotechnology and nanotechnology: mini-review. Molecules 23, 2438 (2018).

    Article  Google Scholar 

  12. Uebe, R. & Schüler, D. Magnetosome biogenesis in magnetotactic bacteria. Nat. Rev. Microbiol. 14, 621–637 (2016).

    Article  CAS  Google Scholar 

  13. Mickoleit, F. & Schüler, D. Generation of multifunctional magnetic nanoparticles with amplified catalytic activities by genetic expression of enzyme arrays on bacterial magnetosomes. Adv. Biosyst. 2, 1700109 (2018).

    Article  Google Scholar 

  14. Mickoleit, F. & Schüler, D. Generation of nanomagnetic biocomposites by genetic engineering of bacterial magnetosomes. Bioinspired Biomim. Nanobiomaterials 8, 86–98 (2018).

    Article  Google Scholar 

  15. Mickoleit, F., Lanzloth, C. & Schüler, D. A versatile toolkit for controllable and highly selective multifunctionalization of bacterial magnetic nanoparticles. Small 16, 1906922 (2020).

    Article  CAS  Google Scholar 

  16. Kuzajewska, D., Wszołek, A., Żwierełło, W., Kirczuk, L. & Maruszewska, A. Magnetotactic bacteria and magnetosomes as smart drug delivery systems: a new weapon on the battlefield with cancer? Biology 9, 102 (2020).

    Article  CAS  Google Scholar 

  17. Boucher, M. et al. Genetically tailored magnetosomes used as MRI probe for molecular imaging of brain tumor. Biomaterials 121, 167–178 (2017).

    Article  CAS  Google Scholar 

  18. Kraupner, A. et al. Bacterial magnetosomes – nature’s powerful contribution to MPI tracer research. Nanoscale 9, 5788–5793 (2017).

    Article  CAS  Google Scholar 

  19. Le Fèvre, R. et al. Enhanced antitumor efficacy of biocompatible magnetosomes for the magnetic hyperthermia treatment of glioblastoma. Theranostics 7, 4618–4631 (2017).

    Article  Google Scholar 

  20. Alphandéry, E. Applications of magnetosomes synthesized by magnetotactic bacteria in medicine. Front. Bioeng. Biotechnol. 2, 5 (2014).

    Google Scholar 

  21. Kolinko, I. et al. Biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene clusters. Nat. Nanotechnol. 9, 193–197 (2014).

    Article  CAS  Google Scholar 

  22. Dziuba, M. V., Zwiener, T., Uebe, R. & Schüler, D. Single-step transfer of biosynthetic operons endows a non-magnetotactic Magnetospirillum strain from wetland with magnetosome biosynthesis. Environ. Microbiol. 22, 1603–1618 (2020).

    Article  CAS  Google Scholar 

  23. Dziuba, M. V. et al. Silent gene clusters encode magnetic organelle biosynthesis in a non-magnetotactic phototrophic bacterium. ISME J. 17, 326–339 (2023).

    Article  CAS  Google Scholar 

  24. Juodeikis, R. Engineering Membranes in Escherichia coli: the Magnetosome, LemA Protein Family and Outer Membrane Vesicles. PhD thesis, Univ. Kent (2016).

  25. Mag-nano-tite: Creating magnetite nanoparticles in E.coli. iGEM https://2016.igem.org/Team:Kent/Description (2016).

  26. iGEM toolkits: magnetosomes. iGEM https://2011.igem.org/Team:Washington/Magnetosomes/Magnet_Toolkit (2011).

  27. Magnetosome formation: experiments & results. iGEM https://2014.igem.org/Team:Kyoto/Project/Magnetosome_Formation#experiments (2014).

  28. Sistrom, W. R. A requirement for sodium in the growth of Rhodopseudomonas spheroides. J. Gen. Microbiol. 22, 778–785 (1960).

    Article  CAS  Google Scholar 

  29. Heyen, U. & Schüler, D. Growth and magnetosome formation by microaerophilic Magnetospirillum strains in an oxygen-controlled fermentor. Appl. Microbiol. Biotechnol. 61, 536–544 (2003).

    Article  CAS  Google Scholar 

  30. Pfennig, N. Rhodopseudomonas acidophila, sp. n., a new species of the budding purple nonsulfur bacteria. J. Bacteriol. 99, 597–602 (1969).

    Article  CAS  Google Scholar 

  31. Moisescu, C., Ardelean, I. I. & Benning, L. G. The effect and role of environmental conditions on magnetosome synthesis. Front. Microbiol. 5, 49 (2014).

    Article  Google Scholar 

  32. Grant, C. R. et al. Distinct gene clusters drive formation of ferrosome organelles in bacteria. Nature 606, 160–164 (2022).

    Article  CAS  Google Scholar 

  33. Silva, K. T. et al. Genome-wide identification of essential and auxiliary gene sets for magnetosome biosynthesis in Magnetospirillum gryphiswaldense. mSystems 5, e00565–20 (2020).

    Article  CAS  Google Scholar 

  34. Li, Y., Katzmann, E., Borg, S. & Schüler, D. The periplasmic nitrate reductase Nap is required for anaerobic growth and involved in redox control of magnetite biomineralization in Magnetospirillum gryphiswaldense. J. Bacteriol. 194, 4847–4856 (2012).

    Article  CAS  Google Scholar 

  35. Li, Y. et al. Cytochrome cd1 nitrite reductase NirS is involved in anaerobic magnetite biomineralization in Magnetospirillum gryphiswaldense and requires NirN for proper d1 heme assembly. J. Bacteriol. 195, 4297–4309 (2013).

    Article  CAS  Google Scholar 

  36. Li, Y., Raschdorf, O., Silva, K. T. & Schüler, D. The terminal oxidase cbb3 functions in redox control of magnetite biomineralization in Magnetospirillum gryphiswaldense. J. Bacteriol. 196, 2552–2562 (2014).

    Article  Google Scholar 

  37. Wang, Q. et al. Iron response regulator protein IrrB in Magnetospirillum gryphiswaldense MSR-1 helps control the iron/oxygen balance, oxidative stress tolerance, and magnetosome formation. Appl. Environ. Microbiol. 81, 8044–8053 (2015).

    Article  CAS  Google Scholar 

  38. Li, Y. et al. The oxygen sensor MgFnr controls magnetite biomineralization by regulation of denitrification in Magnetospirillum gryphiswaldense. BMC Microbiol. 14, 153 (2014).

    Article  Google Scholar 

  39. Qi, L. et al. Fur in Magnetospirillum gryphiswaldense influences magnetosomes formation and directly regulates the genes involved in iron and oxygen metabolism. PLoS ONE 7, e29572 (2012).

    Article  CAS  Google Scholar 

  40. Kolinko, S., Richter, M., Glöckner, F. O., Brachmann, A. & Schüler, D. Single-cell genomics reveals potential for magnetite and greigite biomineralization in an uncultivated multicellular magnetotactic prokaryote. Environ. Microbiol. Rep. 6, 524–531 (2014).

    Article  CAS  Google Scholar 

  41. Popp, F., Armitage, J. P. & Schüler, D. Polarity of bacterial magnetotaxis is controlled by aerotaxis through a common sensory pathway. Nat. Commun. 14, 5398 (2014).

    Article  Google Scholar 

  42. Rong, C. et al. FeoB2 functions in magnetosome formation and oxidative stress protection in Magnetospirillum gryphiswaldense strain MSR-1. J. Bacteriol. 194, 3972–3976 (2012).

    Article  CAS  Google Scholar 

  43. Rong, C. et al. Ferrous iron transport protein B gene (feoB1) plays an accessory role in magnetosome formation in Magnetospirillum gryphiswaldense strain MSR-1. Res. Microbiol. 159, 530–536 (2008).

    Article  CAS  Google Scholar 

  44. Nelson, L. M. & Knowles, R. Effect of oxygen and nitrate on nitrogen fixation and denitrification by Azospirillum brasilense grown in continuous culture. Can. J. Microbiol. 24, 1395–1403 (1978).

    Article  CAS  Google Scholar 

  45. Bergaust, L., Shapleigh, J., Frostegård, Å. & Bakken, L. Transcription and activities of NOx reductases in Agrobacterium tumefaciens: the influence of nitrate, nitrite and oxygen availability. Environ. Microbiol. 10, 3070–3081 (2008).

    Article  CAS  Google Scholar 

  46. Kampschreur, M. J. et al. Metabolic modeling of denitrification in Agrobacterium tumefaciens: a tool to study inhibiting and activating compounds for the denitrification pathway. Front. Microbiol. 3, 370 (2012).

    Article  Google Scholar 

  47. Hershberg, R. & Petrov, D. A. Selection on codon bias. Annu. Rev. Genet. 42, 287–299 (2008).

    Article  CAS  Google Scholar 

  48. Gomes, A. L. C. et al. Genome and sequence determinants governing the expression of horizontally acquired DNA in bacteria. ISME J. 14, 2347–2357 (2020).

    Article  CAS  Google Scholar 

  49. Mickoleit, F. et al. High-yield production, characterization, and functionalization of recombinant magnetosomes in the synthetic bacterium Rhodospirillum rubrum “magneticum”. Adv. Biol. 5, 2101017 (2021).

    Article  CAS  Google Scholar 

  50. Richter, P., Melzer, B. & Müller, F. D. Interacting bactofilins impact cell shape of the MreB-less multicellular Rhodomicrobium vannielii. PLoS Genet. 19, e1010788 (2023).

    Article  CAS  Google Scholar 

  51. Orsi, E., Beekwilder, J., Eggink, G., Kengen, S. W. M. & Weusthuis, R. A. The transition of Rhodobacter sphaeroides into a microbial cell factory. Biotechnol. Bioeng. 118, 531–541 (2021).

    Article  CAS  Google Scholar 

  52. Li, M., Ning, P., Sun, Y., Luo, J. & Yang, J. Characteristics and application of Rhodopseudomonas palustris as a microbial cell factory. Front. Bioeng. Biotechnol. 10, 897003 (2022).

    Article  Google Scholar 

  53. Strittmatter, W., Weckesser, J., Salimath, P. V. & Galanos, C. Nontoxic lipopolysaccharide from Rhodopseudomonas sphaeroides ATCC 17023. J. Bacteriol. 155, 153–158 (1983).

    Article  CAS  Google Scholar 

  54. Lin, T. L. et al. Like cures like: pharmacological activity of anti-inflammatory lipopolysaccharides from gut microbiome. Front. Pharmacol. 11, 554 (2020).

    Article  CAS  Google Scholar 

  55. Schultheiss, D. & Schüler, D. Development of a genetic system for Magnetospirillum gryphiswaldense. Arch. Microbiol. 179, 89–94 (2003).

    Article  CAS  Google Scholar 

  56. Chen, S., Zhou, Y., Chen, Y. & Gu, J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884–i890 (2018).

    Article  Google Scholar 

  57. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).

    Article  CAS  Google Scholar 

  58. Kearse, M. et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinforma. Appl. 28, 1647–1649 (2012).

    Article  Google Scholar 

  59. Contreras-Moreira, B. & Vinuesa, P. GET_HOMOLOGUES, a versatile software package for scalable and robust microbial pangenome analysis. Appl. Environ. Microbiol. 79, 7696–7701 (2013).

    Article  CAS  Google Scholar 

  60. Waskom, M. seaborn: statistical data visualization. J. Open Source Softw. 6, 3021 (2021).

    Article  Google Scholar 

  61. Schüler, D., Uhl, R., & Bäuerlein, E. A simple light scattering method to assay magnetism in Magnetospirillum gryphiswaldense. FEMS Microbiol. Lett 132, 139–145 (1995).

    Article  Google Scholar 

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Acknowledgements

This study was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant no. 692637 to D.S.). We are grateful to M. Schüler and S. Geimer for their help with electron microscopy. Electron microscopy performed at University of Pannonia was supported by the National Research, Development and Innovation Office (Hungary; grant no. RRF-2.3.1-21-2022-00014 to M.P.). We also thank A. Hübner, L. Borgert, J. Kachel and B. Melzer for technical assistance.

Author information

Authors and Affiliations

  1. Department of Microbiology, Faculty of Biology, Chemistry and Geosciences, University of Bayreuth, Bayreuth, Germany

    Marina V. Dziuba, Frank-Dietrich Müller & Dirk Schüler

  2. ELKH-PE Environmental Mineralogy Research Group, Veszprém, Hungary

    Mihály Pósfai

  3. Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprém, Hungary

    Mihály Pósfai

Authors
  1. Marina V. Dziuba
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  2. Frank-Dietrich Müller
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  3. Mihály Pósfai
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  4. Dirk Schüler
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Contributions

D.S. and M.V.D. conceived, conceptualized and designed the experiments. M.V.D. performed the experiments, measurements and data analyses. F.-D.M. conducted the magnetosome gene transfer to Rhodomicrobium vannielii and analysed the phenotype in the strain. M.P. carried out the crystallography analysis. M.V.D. and D.S. wrote the original draft along with review and editing. D.S. carried out the funding acquisition, project administration and supervision. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Dirk Schüler.

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The authors declare no competing interests.

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Nature Nanotechnology thanks Donna Goldhawk and Jie Tian for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Crystallographic analysis of the magnetosomes produced by B. viridis MAG.

(a) and (e) BF TEM micrographs of the magnetosome chain. HAADF image (b) and elemental maps (c, d-i) of the boxed area in (a). (d-ii) EDS spectra of the areas marked in (d-i), indicating that flake-like particles also contain Fe and O. (f) HRTEM image of the magnetosome chain from the boxed area in (e) with FFT of the twinned particle in the center, with one of its parts in [112] zone-axis orientation of magnetite.

Extended Data Fig. 2 Crystallographic analysis of the magnetosomes produced by Rhodoblastus acidophilus MAG.

(a) BF TEM micrograph of the cells. (b) HAADF image of the boxed area in (a) with (c–e) close-up HAADF image and elemental maps of the boxed region in (b). (e-ii) EDS spectra of the areas marked in (e-i). Fe-O-P-rich particles in area #1 likely represent ferrosomes, whereas particles in area #2 are magnetite magnetosomes. (f) and (g) HRTEM images with FFTs of the indicated particles. The particle in (f) and the lower, small particle in (g) are magnetite in [130] and [110] zone-axis orientations, respectively, whereas the upper particle in (g) is amorphous (a putative ferrosome).

Extended Data Fig. 3 Crystallographic analysis of the magnetosomes produced by A. brasilense MAG.

(a) BF TEM micrograph of the cells with magnetosomes. (b) HRTEM image of the magnetosomes from the boxed area in (a) with FFTs of the magnetosomes in zone-axis orientations consistent with magnetite. (c) EDS spectrum of the magnetosome marked with an asterisk in (b). (d-f) HAADF image and elemental maps of the magnetosome chain.

Supplementary information

Supplementary Information

Supplementary Figs. 1–6 and Tables 1–4.

Reporting Summary

Supplementary Video 1

Magnetic response of Rhodomicrobium vannielii MAG culture.

Source data

Source Data Fig. 2

Magnetosome diameter measurements (in nanometres) for all magnetized strains and M. gryphiswaldense, used to create the violin plot in Fig. 2h, along with the statistical summary of the data.

Source Data Fig. 4

Source data for Fig. 4a–d: OD660, Cmag values, magnetosome numbers per cell and diameter measurements (in nanometres).

Source Data Fig. 6

G+C% differences between the strains calculated using whole genomes along with magnetosome core diameters (as in Source Data Fig. 2h) and magnetosome numbers per cell.

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Dziuba, M.V., Müller, FD., Pósfai, M. et al. Exploring the host range for genetic transfer of magnetic organelle biosynthesis. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01500-5

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