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Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome structures

View ORCID ProfileAshley V. Makela, Melissa A. Schott, Cody Madsen, Emily Greeson, View ORCID ProfileChristopher H. Contag
doi: https://doi.org/10.1101/2021.12.03.471101
Ashley V. Makela
1Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
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Melissa A. Schott
2Homer Stryker M.D. School of Medicine, Western Michigan University, Kalamazoo, MI, USA
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Cody Madsen
1Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
3Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA
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Emily Greeson
1Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
4Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
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Christopher H. Contag
1Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
3Department of Biomedical Engineering, Michigan State University, East Lansing, MI, USA
4Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA
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  • For correspondence: contagch@msu.edu
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ABSTRACT

Iron nanoparticles used as imaging contrast agents can help differentiate between normal and diseased tissue, or track cell movement and localize pathologies. Magnetic particle imaging (MPI) is an imaging modality that uses the magnetic properties of iron nanoparticles to provide specific, quantitative and sensitive imaging data. MPI signals depend on the size, structure and composition of the nanoparticles; MPI-tailored nanoparticles have been developed by modifying these properties. Magnetotactic bacteria produce magnetosomes which mimic synthetic nanoparticles, and thus comprise a living contrast agent in which nanoparticle formation can be modified by mutating genes. Specifically, genes that encode proteins critical to magnetosome formation and regulation, such as mamJ which helps with filament turnover. Deletion of mamJ in Magnetospirillum gryphiswaldense, MSR-1 led to clustered magnetosomes instead of the typical linear chains. Here we examined the effects of this magnetosome structure and revealed improved MPI signal and resolution from clustered magnetosomes compared to linear chains. Bioluminescent MSR-1 with the mamJ deletion were injected intravenously into tumor-bearing and healthy mice and imaged using both in vivo bioluminescence imaging (BLI) and MPI. BLI revealed the location and viability of bacteria which was used to validate localization of MPI signals. BLI identified the viability of MSR-1 for 24 hours and MPI detected iron in the liver and in multiple tumors. Development of living contrast agents offers new opportunities for imaging and therapy by using multimodality imaging to track the location and viability of the therapy and the resulting biological effects.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 04, 2021.
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Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome structures
Ashley V. Makela, Melissa A. Schott, Cody Madsen, Emily Greeson, Christopher H. Contag
bioRxiv 2021.12.03.471101; doi: https://doi.org/10.1101/2021.12.03.471101
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Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome structures
Ashley V. Makela, Melissa A. Schott, Cody Madsen, Emily Greeson, Christopher H. Contag
bioRxiv 2021.12.03.471101; doi: https://doi.org/10.1101/2021.12.03.471101

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