Survival Strategies of Borrelia burgdorferi
Insights into the resilience and challenges of Lyme disease bacteria.
Christine Jacobs-Wagner, J. Zhang, C. N. Takacs, J. W. McCausland, E. Mueller, J. Buron, Y. Thappeta, J. Wachter, P. A. Rosa
― 6 min read
Table of Contents
Lyme disease is caused by a type of bacteria called Borrelia Burgdorferi, mainly found in North America and Europe. This bacteria is transmitted to humans through the bite of infected ticks. While ticks are one of the primary hosts, humans are considered "dead-end" hosts because the bacteria do not spread from humans to other ticks. The lifecycle of this bacteria involves various animals, mainly ticks and small mammals.
Lifecycle of Borrelia burgdorferi
Borrelia burgdorferi has a complex lifecycle. It begins when young ticks, known as larvae, feed on infected animals, acquiring the bacteria. Once they feed, the bacteria live in the tick's stomach until the tick matures into a nymph. The nymph then feeds on another animal, where the bacteria can enter a new host. Unlike many other bacteria, Borrelia burgdorferi can survive for long periods without food.
Starvation
The Issue ofBacteria often face tough conditions that include scarcity of food. Borrelia burgdorferi is no different. During periods of starvation, it can still survive. Studies show that even in harsh conditions, many bacteria can remain alive for extended periods without growing. Some bacteria can hold on to their ability to reproduce even after months of starvation.
In laboratory conditions, it is common to study bacteria in a state where they are not actively growing. This phase is called "Stationary Phase," where bacteria cease to multiply but might still be alive. Many bacteria can stay in this state and return to normal growth when food becomes available.
However, Borrelia burgdorferi has unique traits that differentiate it from other bacteria. It is a parasite that requires a host. It cannot live independently outside of its tick or animal hosts. Its survival depends on the ability to adapt to these hosts and their environments.
Observations in Laboratory Cultures
In laboratory settings, researchers grow Borrelia burgdorferi in a specialized nutrient-rich medium. This medium allows the bacteria to thrive and reach high population densities. However, when researchers induce starvation by switching to a less nutrient-rich environment, the bacteria stop growing and can lose their ability to reproduce.
In experiments, researchers examined how these bacteria behave in stationary phase. They found that Borrelia burgdorferi cells lose their ability to grow despite appearing healthy under a microscope. The initial health of the cells can be misleading because even when the cells look fine, they can’t reproduce effectively.
Cell Health vs. Growth Ability
During these experiments, scientists often measure cell health using a dye called propidium iodide. This dye can indicate whether the cell membrane is intact. However, researchers noticed that just because a cell appeared healthy didn’t mean it could reproduce. Cells that were intact still lost their ability to grow when they were placed in conditions that typically promote reproduction.
For instance, when researchers analyzed how many of these cells could still grow into colonies after being placed in fresh nutrients, they found that many could not. After just a few days of starvation, the ability to reproduce dropped significantly.
PH on Cell Growth
Effects ofThe bacteria also face changes in their environment while in the laboratory. One of the challenges they face is changes in acid levels (pH). When the pH is lowered, experiments showed that the cell's ability to grow was affected. When cells were placed in a medium with a lower pH, they still looked healthy, but they gradually lost their ability to grow and form colonies.
This finding highlights that both starvation and acidic conditions can negatively affect the growth of Borrelia burgdorferi. Researchers confirmed that placing the bacteria in nutrient-deficient conditions with a lowered pH led to significant drops in their growth capabilities.
Genetic Changes in Stationary Phase
Another important aspect of the research was understanding how Borrelia burgdorferi manages its genetic material during starvation. It was noted that as the bacteria entered stationary phase, there were observable changes in the distribution of their DNA. The presence of the bacteria's DNA became less uniform, leading researchers to conclude that the bacteria might be losing genetic material.
The core genetic material is essential for the bacteria’s ability to reproduce. As the cells lost specific genetic elements, they became less capable of growing. This genetic loss was particularly concerning because it indicates a direct link between their survival mechanisms and their ability to reproduce when conditions improve.
Plasmid Loss
In addition to the loss of core genetic elements, researchers also looked at Plasmids. Plasmids are smaller circles of DNA that can carry genes that provide various advantages to bacteria, such as antibiotic resistance. In laboratory settings, it became evident that Borrelia burgdorferi was losing plasmids during prolonged periods in stationary phase.
The loss of plasmids is a well-known phenomenon with other bacteria, but researchers found that in the case of Borrelia burgdorferi, this loss occurred more frequently in stationary phase than during active growth. The fact that they could lose plasmids while still maintaining some genetic material raises questions about how this affects their ability to thrive in their natural environments versus the laboratory.
Comparison with Natural Environments
One might wonder how this behavior in the laboratory compares to what happens in nature, particularly within ticks. Researchers have conducted studies on ticks that have remained unfed for prolonged periods, even up to 14 months. In those cases, they found that the population of Borrelia burgdorferi remained stable.
Unlike in the laboratory, where plasmid loss and genetic material changes were observed, ticks usually maintained their spirochete levels, indicating that the bacteria were still viable. This suggests that the ticks provide an environment that sustains the bacteria’s ability to survive over long periods without a host.
Implications for Research
The findings from these studies have significant implications for how researchers understand Borrelia burgdorferi and its behavior. For one, it is essential to be cautious in interpreting results based on cell membrane integrity alone. Just because a cell looks healthy does not ensure that it can reproduce when conditions allow.
Moreover, understanding the loss of plasmids and genetic material during stationary phase can inform better practices in laboratory protocols, especially for those involved in genetic manipulation of Borrelia burgdorferi. Managing the conditions in which these bacteria are cultured can help mitigate the loss of important genetic elements and improve the quality of experimental results.
Conclusion
Overall, the studies conducted illustrate the unique challenges that Borrelia burgdorferi faces in both natural and laboratory settings. While it can survive in tough conditions, the ability to reproduce is significantly affected by environmental factors, such as nutrient availability and pH levels. Understanding these dynamics can help in developing better strategies for studying this important pathogen and its role in Lyme disease transmission.
This exploration of the bacteria's lifecycle, survival mechanisms, and genetic changes underlines the importance of further research into how we can better understand and manage Lyme disease.
Title: Borrelia burgdorferi loses essential genetic elements and cell proliferative potential during stationary phase in culture but not in the tick vector.
Abstract: The Lyme disease agent Borrelia burgdorferi is a polyploid bacterium with a segmented genome in which both the chromosome and over 20 distinct plasmids are present in multiple copies per cell. This pathogen can survive at least nine months in its tick vector in an apparent dormant state between blood meals, without losing cell proliferative capability when re-exposed to nutrients. Cultivated B. burgdorferi cells grown to stationary phase or resuspended in nutrient-limited media are often used to study the effects of nutrient deprivation. However, a thorough assessment of the spirochetes ability to recover from nutrient depletion has been lacking. Our study shows that starved B. burgdorferi cultures rapidly lose cell proliferative. Loss of genetic elements essential for cell proliferation contributes to the observed proliferative defect in stationary phase. The gradual decline in copies of genetic elements is not perfectly synchronized between chromosomes and plasmids, generating cells that harbor one or more copies of the essential chromosome but lack all copies of one or more non-essential plasmids. This phenomenon likely contributes to the well-documented issue of plasmid loss during in vitro cultivation of B. burgdorferi. In contrast, B. burgdorferi cells from ticks starved for 14 months showed no evidence of reduced cell proliferative ability or plasmid loss. Beyond their practical implications for studying B. burgdorferi, these findings suggest that the midgut of the tick vector offers a unique environment that supports the maintenance of B. burgdorferis segmented genome and cell proliferative potential during periods of tick fasting. ImportanceBorrelia burgdorferi causes Lyme disease, a prevalent tick-borne illness. B. burgdorferi must survive long periods (months to a year) of apparent dormancy in the midgut of the tick vector between blood meals. Resilience to starvation is a common trait among bacteria. However, this study reveals that in laboratory cultures, B. burgdorferi poorly endures starvation and rapidly loses viability. This decline is linked to a gradual loss of genetic elements required for cell proliferation. These results suggest that the persistence of B. burgdorferi in nature is likely shaped more by unique environmental conditions in the midgut of the tick vector than by a general innate ability of this bacterium to endure nutrient deprivation.
Authors: Christine Jacobs-Wagner, J. Zhang, C. N. Takacs, J. W. McCausland, E. Mueller, J. Buron, Y. Thappeta, J. Wachter, P. A. Rosa
Last Update: 2024-10-28 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.10.28.620338
Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.28.620338.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.