ライム病菌が利用するマンガンの二面性(Manganese is Lyme Disease’s Double-Edge Sword)

2025-11-13 ノースウェスタン大学

<関連情報>

• https://news.northwestern.edu/stories/2025/11/manganese-is-lyme-diseases-double-edge-sword
• https://journals.asm.org/doi/10.1128/mbio.02824-25

EPR分光法はライム病病原体ボレリア・ブルグドルフェリにおける抗酸化マンガン防御を明らかにする EPR spectroscopy reveals antioxidant manganese defenses in the Lyme disease pathogen Borrelia burgdorferi

Andrés F. Londoño, Ajay Sharma, Venkatesan Kathiresan, Jared Sealy, Robert P. Volpe, Cene Gostinčar, Utpal Pal, J. Stephen Dumler, Brian M. Hoffman, Michael J. Daly
mBio  Published:13 November 2025
DOI:https://doi.org/10.1128/mbio.02824-25

ABSTRACT

Oxidative stress defense in aerobic bacteria relies on Mn-superoxide dismutase (MnSOD) and antioxidant Mn-metabolite complexes (H-Mn) to quench superoxide radicals (O₂^•-). We investigated these antioxidant systems in Borrelia burgdorferi, the Mn-accumulating, Fe-independent Lyme disease pathogen. Using electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) spectroscopies, we tracked Mn²⁺ partitioning between enzyme-bound (L-Mn) and metabolite-bound (H-Mn) pools in spirochetes at exponential and stationary phases. Results show that MnSOD neutralizes extracellular O₂^•- generated by γ-irradiation (a model for host immune attack); H-Mn neutralizes cytoplasmic O₂^•- and is a reservoir of labile Mn²⁺ for metalating Mn-dependent enzymes. MnCl₂ supplementation in log phase B. burgdorferi restored radioresistance in ΔMnSOD mutants via H-Mn hyperaccumulation but induced toxicity in older, stationary phase cells as metabolites became depleted. These findings support an expanded oxidative-stress model in which H-Mn complements MnSOD and positions Mn homeostasis as a therapeutic target. Our approach highlights the utility of EPR and ENDOR in studying Mn-dependent pathogens.