Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology
ABSTRACT The bacterium responsible for Lyme disease, Borrelia burgdorferi, accumulates high levels of manganese without iron and possesses a polyploid genome, characteristics suggesting potential extreme resistance to radiation. Contrary to expectations, we report that wild-type B. burgdorferi B31 c...
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American Society for Microbiology
2025-02-01
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03131-24 |
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| author | Andrés F. Londoño Ajay Sharma Jared Sealy Vipin S. Rana Shelby D. Foor Vera Y. Matrosova Elena K. Gaidamakova Robert P. Volpe Michael J. Daly Brian M. Hoffman Utpal Pal J. Stephen Dumler |
| author_facet | Andrés F. Londoño Ajay Sharma Jared Sealy Vipin S. Rana Shelby D. Foor Vera Y. Matrosova Elena K. Gaidamakova Robert P. Volpe Michael J. Daly Brian M. Hoffman Utpal Pal J. Stephen Dumler |
| author_sort | Andrés F. Londoño |
| collection | DOAJ |
| description | ABSTRACT The bacterium responsible for Lyme disease, Borrelia burgdorferi, accumulates high levels of manganese without iron and possesses a polyploid genome, characteristics suggesting potential extreme resistance to radiation. Contrary to expectations, we report that wild-type B. burgdorferi B31 cells are radiosensitive, with a gamma-radiation survival limit for 106 wild-type cells of <1 kGy. Thus, we explored B. burgdorferi radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn2+ present as antioxidant Mn2+ metabolite complexes (H-Mn). The spirochetes displayed relatively low levels of H-Mn, in stark contrast to the extremely radiation-resistant Deinococcus radiodurans. The H-Mn content as revealed by EPR spectroscopy is sufficiently sensitive to detect small changes in radiosensitivity among B. burgdorferi strains. However, B. burgdorferi cells are significantly more sensitive than predicted by EPR, implicating their linear genome architecture as an additional explanation for radiosensitivity. We then explored the influence of the Mn2+-decapeptide-phosphate antioxidant complex MDP, known to shield proteins during irradiation, and showed that treatment with MDP preserves B. burgdorferi’s epitopes at 5 kGy irradiation, which crucially prevents cell proliferation. This finding defines some of the pivotal mechanisms that B. burgdorferi evolved to survive oxidative conditions experienced with tick and mammal immune responses. These observations also provide an opportunity for innovative vaccine development strategies employing ionizing radiation to disrupt the B. burgdorferi genome, while maintaining antigenic potency. These fresh insights extend our understanding of the unique biology of B. burgdorferi and open new avenues for considering novel whole-cell Lyme disease vaccines using MDP and irradiation-based inactivation.IMPORTANCEThe study highlights that electron paramagnetic resonance (EPR) spectroscopy is sufficiently sensitive to detect small differences in radiation resistance among Borrelia burgdorferi strains based on their population of Mn2+-metabolite complexes (H-Mn). B. burgdorferi appears to have evolved a system not to protect from irradiation, but presumably to protect from oxidative stress when cyclically transmitted from tick to mammalian host and back. These data also suggest a path forward in the development of novel vaccines against spirochete infections, including Lyme disease, through preparation involving the synthetic Mn2+-decapeptide-phosphate antioxidant complex MDP to provide B. burgdorferi epitope protection during sterilizing gamma-irradiation that eliminates growth. Given the current lack of effective whole-cell vaccines for Lyme disease, this research identifies a potential strategy for developing alternative radiation-inactivated, yet highly effective vaccines. |
| format | Article |
| id | doaj-art-f2d88c5fc1be480c819fe33e4aa7d84d |
| institution | Kabale University |
| issn | 2150-7511 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
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| series | mBio |
| spelling | doaj-art-f2d88c5fc1be480c819fe33e4aa7d84d2025-02-05T14:00:48ZengAmerican Society for MicrobiologymBio2150-75112025-02-0116210.1128/mbio.03131-24Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiologyAndrés F. Londoño0Ajay Sharma1Jared Sealy2Vipin S. Rana3Shelby D. Foor4Vera Y. Matrosova5Elena K. Gaidamakova6Robert P. Volpe7Michael J. Daly8Brian M. Hoffman9Utpal Pal10J. Stephen Dumler11School of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USADepartment of Chemistry, Northwestern University, Evanston, Illinois, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USADepartment of Veterinary Medicine, University of Maryland, College Park, Maryland, USADepartment of Veterinary Medicine, University of Maryland, College Park, Maryland, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USADepartment of Chemistry, Northwestern University, Evanston, Illinois, USADepartment of Veterinary Medicine, University of Maryland, College Park, Maryland, USASchool of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland, USAABSTRACT The bacterium responsible for Lyme disease, Borrelia burgdorferi, accumulates high levels of manganese without iron and possesses a polyploid genome, characteristics suggesting potential extreme resistance to radiation. Contrary to expectations, we report that wild-type B. burgdorferi B31 cells are radiosensitive, with a gamma-radiation survival limit for 106 wild-type cells of <1 kGy. Thus, we explored B. burgdorferi radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn2+ present as antioxidant Mn2+ metabolite complexes (H-Mn). The spirochetes displayed relatively low levels of H-Mn, in stark contrast to the extremely radiation-resistant Deinococcus radiodurans. The H-Mn content as revealed by EPR spectroscopy is sufficiently sensitive to detect small changes in radiosensitivity among B. burgdorferi strains. However, B. burgdorferi cells are significantly more sensitive than predicted by EPR, implicating their linear genome architecture as an additional explanation for radiosensitivity. We then explored the influence of the Mn2+-decapeptide-phosphate antioxidant complex MDP, known to shield proteins during irradiation, and showed that treatment with MDP preserves B. burgdorferi’s epitopes at 5 kGy irradiation, which crucially prevents cell proliferation. This finding defines some of the pivotal mechanisms that B. burgdorferi evolved to survive oxidative conditions experienced with tick and mammal immune responses. These observations also provide an opportunity for innovative vaccine development strategies employing ionizing radiation to disrupt the B. burgdorferi genome, while maintaining antigenic potency. These fresh insights extend our understanding of the unique biology of B. burgdorferi and open new avenues for considering novel whole-cell Lyme disease vaccines using MDP and irradiation-based inactivation.IMPORTANCEThe study highlights that electron paramagnetic resonance (EPR) spectroscopy is sufficiently sensitive to detect small differences in radiation resistance among Borrelia burgdorferi strains based on their population of Mn2+-metabolite complexes (H-Mn). B. burgdorferi appears to have evolved a system not to protect from irradiation, but presumably to protect from oxidative stress when cyclically transmitted from tick to mammalian host and back. These data also suggest a path forward in the development of novel vaccines against spirochete infections, including Lyme disease, through preparation involving the synthetic Mn2+-decapeptide-phosphate antioxidant complex MDP to provide B. burgdorferi epitope protection during sterilizing gamma-irradiation that eliminates growth. Given the current lack of effective whole-cell vaccines for Lyme disease, this research identifies a potential strategy for developing alternative radiation-inactivated, yet highly effective vaccines.https://journals.asm.org/doi/10.1128/mbio.03131-24Lyme diseaseBorreliaDeinococcusirradiated vaccinegamma-radiationMDP |
| spellingShingle | Andrés F. Londoño Ajay Sharma Jared Sealy Vipin S. Rana Shelby D. Foor Vera Y. Matrosova Elena K. Gaidamakova Robert P. Volpe Michael J. Daly Brian M. Hoffman Utpal Pal J. Stephen Dumler Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology mBio Lyme disease Borrelia Deinococcus irradiated vaccine gamma-radiation MDP |
| title | Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology |
| title_full | Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology |
| title_fullStr | Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology |
| title_full_unstemmed | Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology |
| title_short | Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology |
| title_sort | borrelia burgdorferi radiosensitivity and mn antioxidant content antigenic preservation and pathobiology |
| topic | Lyme disease Borrelia Deinococcus irradiated vaccine gamma-radiation MDP |
| url | https://journals.asm.org/doi/10.1128/mbio.03131-24 |
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