Lyme
If you've lived in the north eastern United States then you've likely been warned about the dangers of ticks and Lyme disease. Lyme disease is caused by bacteria from black tick bites and can be spread between mammals and ticks in a cyclic pattern. It starts with symptoms such as rash, headache, fatigue, and fever but untreated it can spread to joints, the heart, and the nervous system. We are warned about the danger and told to wear bug spray and try to spot ticks before they latch, but other than wearing tick repellent and being vigilant what can we do about it?
In the United States, Lyme is caused by a bacterium called Borrelia burgdorferi, a pathogenic parasite in the shape of spirochete (spiral shaped bacterium that is often a serious pathogen for humans). B. burgdorferi has a polyploid genome (more than 2 paired sets of chromosomes) and accumulates high levels of manganese (Mn) without iron. Based on research of other bacterium this would suggest an extreme resistance to radiation. However in 2024 this paper, Borrelia burgdorferi radiosensitivity and Mn antioxidant content: antigenic preservation and pathobiology, authored by Andrés F. Londoño and others, found otherwise. It is believed that the system of this cell evolved to protect from the cyclic exposure to oxidative conditions within tick and mammal immune responses as opposed to radiation protection.
Graphic of B. burgdorferi (linked here)
Mn Content
These Mn2+ complexes act as Mn antioxidants that accumulate in radiation resistant cells. Mn that accumulates as H-Mn has been shown to greatly enhance radiation survivability of polyploid cells. The H-Mn protects the DNA-repair enzymes from reactive oxygen species (ROS). This enhances the ability for mending DNA breaks caused by ionizing radiation.
Back to B. burgdorferi
The authors found that wild-type B. burgdorferi cells were sensitive to radiation. This radiosensitivity was explored through electron paramagnetic resonance (EPR) spectroscopy by assessing the fraction of Mn2+ present as antioxidant metabolite complexes (H-Mn). They found that in contrast to radiation resistant bacteria, the cells of B. burgdorferi showed low levels of H-Mn content, suggesting they would instead be radiosensitive. Shown below in Figure 2, you can see throughout all graphs, that the control groups (no irradiation) had much higher levels of B. burgdorferi content. For this figure it is important to note that Gy (grays) is the unit for measurement of the absorbed dose of radiation.
Fig 2 Re-growth assessed using dark-field microscopy (A and B) and DNA concentration by qPCR (C and D) of B. burgdorferi irradiated with or without MDP
In addition to these findings, they also found that it was even more radio-sensitive than the EPR spectroscopy predicted. The explanation they provided for this additional sensitivity is in the linear architecture of the cell's genome. Because of this they explored the effect of treatment with the Mn2+-decapeptide-phosphate antioxidant complex otherwise known as MDP. MDP is known to protect surface proteins, while leaving the DNA and RNA inside unprotected. They found that treatment with MDP preserved the cells epitopes (the part of the antigen that is recognized by the body's immune system) which causes a decrease in cell growth. To observe this they conducted protein immunoblot analysis of 2D gel electrophoresis. In the images of figure 4 pixel density correlates to intensity of the protein band signals, higher density means less light is transmitted, aka higher pixel density correlates to higher protein expression. In panel A of figure 4 we can see that in the images, at the same levels of radiation, the cells treated with MDP had a higher pixel density even at short exposure times. This is emphasized in panel B where the images showing results for around the minute mark are displayed, and we can see the increased density side by side. This displays that when cells were irradiated in the presence of MDP they showed higher antigen preservation then without MDP.
Fig 4 Protein immunoblot analysis of 2D gel electrophoresis for B. burgdorferi (A) Analysis of the median pixel density versus exposure time. (B) displays irradiation exposures, MDP treatment, and exact exposure time for each image.
So, why is this important? It shows potential for vaccine development. These results indicate a possible strategy for using ionizing radiation to disrupt the genome while maintaining the antigenic effects of the vaccine, not only of B. burgdorferi but other spirochetes as well. This would protect just enough of the bacterial cells to allow the body to identify and attack the cells, creating an established immune response, while leaving the genetic material available to be destroyed by radiation. The strategy of using a whole-cell irradiated vaccine using MDP is preferred to the traditional subunit method which is developmentally time consuming. This would allow development and production of a vaccine to proceed at a much faster pace than would have been previously possible.
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