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Contrary to expectations, we report that wild-type\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      B31 cells are radiosensitive, with a gamma-radiation survival limit for 10\n                      <jats:sup>6<\/jats:sup>\n                      wild-type cells of &lt;1 kGy. Thus, we explored\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn\n                      <jats:sup>2+<\/jats:sup>\n                      present as antioxidant Mn\n                      <jats:sup>2+<\/jats:sup>\n                      metabolite complexes (H-Mn). The spirochetes displayed relatively low levels of H-Mn, in stark contrast to the extremely radiation-resistant\n                      <jats:italic>Deinococcus radiodurans<\/jats:italic>\n                      . The H-Mn content as revealed by EPR spectroscopy is sufficiently sensitive to detect small changes in radiosensitivity among\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      strains. However,\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      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 Mn\n                      <jats:sup>2+<\/jats:sup>\n                      -decapeptide-phosphate antioxidant complex MDP, known to shield proteins during irradiation, and showed that treatment with MDP preserves\n                      <jats:italic>B. burgdorferi\u2019s<\/jats:italic>\n                      epitopes at 5 kGy irradiation, which crucially prevents cell proliferation. This finding defines some of the pivotal mechanisms that\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      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\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      genome, while maintaining antigenic potency. These fresh insights extend our understanding of the unique biology of\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and open new avenues for considering novel whole-cell Lyme disease vaccines using MDP and irradiation-based inactivation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The study highlights that electron paramagnetic resonance (EPR) spectroscopy is sufficiently sensitive to detect small differences in radiation resistance among\n                        <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                        strains based on their population of Mn\n                        <jats:sup>2+<\/jats:sup>\n                        -metabolite complexes (H-Mn).\n                        <jats:italic>B. burgdorferi<\/jats:italic>\n                        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 Mn\n                        <jats:sup>2+<\/jats:sup>\n                        -decapeptide-phosphate antioxidant complex MDP to provide\n                        <jats:italic>B. burgdorferi<\/jats:italic>\n                        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.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03131-24","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T09:00:21Z","timestamp":1735290021000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>Borrelia burgdorferi<\/i>\n                    radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4703-1387","authenticated-orcid":true,"given":"Andr\u00e9s F.","family":"Londo\u00f1o","sequence":"first","affiliation":[{"name":"School of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS)","place":["Bethesda, USA"]},{"name":"Henry M. 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