radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology.

The bacterium responsible for Lyme disease, , 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 B31 cells are radiosensitive, with a gamma-radiation survival limit for 10 wild-type cells of <1 kGy. Thus, we explored radiosensitivity through electron paramagnetic resonance (EPR) spectroscopy by quantitating the fraction of Mn present as antioxidant Mn metabolite complexes (H-Mn). The spirochetes displayed relatively low levels of H-Mn, in stark contrast to the extremely radiation-resistant . The H-Mn content as revealed by EPR spectroscopy is sufficiently sensitive to detect small changes in radiosensitivity among strains. However, 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-decapeptide-phosphate antioxidant complex MDP, known to shield proteins during irradiation, and showed that treatment with MDP preserves epitopes at 5 kGy irradiation, which crucially prevents cell proliferation. This finding defines some of the pivotal mechanisms that 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 genome, while maintaining antigenic potency. These fresh insights extend our understanding of the unique biology of 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 strains based on their population of Mn-metabolite complexes (H-Mn). 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-decapeptide-phosphate antioxidant complex MDP to provide 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.