Borrelia burgdorferi and Lyme Disease Detection

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Overview

Borrelia burgdorferi is a bacterial eubacterial phylum spirochaete and a tick borne parasite. It is one of the known causative agents for Lyme Disease. Borrelia burgdorferi was named after Willy Burgdorfer who first isolated the bacteria in 1982. The spirochete is a flat wave shape that is commonly 0.3 micrometers in width and ranges from 5 to 20 micrometers in length. It has both an outer and inner membrane with a thin layer of peptidoglycan separating the membranes. Seven to eleven bundled periplasmic flagella reside within the membranes and allow the bacterium to move through a highly viscosity medium, which increases its virulence factor. The flagellar filaments wrap around the cell and rotate in order to help the flagellar motor propel the bacteria in a signature corkscrew motion. The doubling time of the bacteria ranges from 24 to 48 hours. Borrelia burgdorferi is different from common pathogenic bacteria because it lacks the common virulence factors like toxins, a specialized secretion system, and lipopolysaccharides. The bacteria lacks common biosynthetic abilities and heavily relies on its host for nutrients and other factors for its survival.

This illustration depicts a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus agalactiae (group B Streptococcus) bacteria. The photo credit for this image belongs to Alissa Eckert, who is a medical illustrator at the CDC.

By Roya Best

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Genetics

The genome of Borrelia burgdorferi is a linear chromosome with many smaller plasmids that are both linear and circular. The linear chromosome is about 950 kb and the linear and circular plasmids range from 9 to 62 kb, which all encode 853 genes. The genome of Borrelia burgdorferi was the third ever genome sequenced. Linear chromosomes are not common in bacteria, however, in Borrelia burgdorferi it seems to provide an advantage that has continued to allow the linear chromosome to persist. The Borrelia burgdorferi genetic sequence shows that the flagella are hidden between the two membranes compared to other organisms that have it externally radiating outward. The flagella are strategically positioned in order to provide Borrelia burgdorferi an advantage in hiding from the host immune system, as this is critical in its survival.

Borrelia burgdorferi lacks the classic genes to synthesize amino acids, fatty acids, enzyme cofactors, and nucleotides. It takes advantage of its host and obtains these important materials. The inability to synthesize these things is likely lost in coevolution with ticks and other hosts. Additionally, Borrelia burgdorferi lacks the genes to use the citric acid cycle, oxidative phosphorylation, and cellular biosynthesis. Borrelia burgdorferi however has the genes for and derives its energy from glycolysis and fermentation of sugars.

Borrelia burgdorferi interacts with platelets, endothelial cells, chondrocytes, and extracellular matrix when infecting a host. These interactions inhibit the proper function of various mechanisms in these infected areas. This leads to the symptoms of Lyme Disease.

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Lyme Disease History and Overview

Lyme Disease is an enzootic vector-borne disease that is transmitted by Ixodes tick. Lyme Disease was first discovered by Doctor Alan Steere in 1977 when he noticed that people were being infected with an unknown pathogen in the same geographic location during the same time of the year presenting with the same symptoms. The first confirmed case was in Lyme, Connecticut, thus providing the name of the Disease. In 1981 it was finally discovered that Borrelia genus bacteria were the causative agents of Lyme Disease.

There are a few Borrelia species that can cause Lyme Disease, however, Borrelia burgdorferi is the most common in the US. Lyme Disease is the leading vector-borne disease in the US. There are an estimated 476,000 cases each year of Lyme Disease in the US according to numbers from 2010 to 2018. However, this is most likely an underestimate because Lyme Disease is difficult to diagnose. Lyme Disease is endemic to the US, Europe, and Asia. Most cases are reported during the Spring and Summer months due to the life cycle of the reservoir, the Ixodes ticks. Common animals that can become infected with Borrelia burgdorferi are white-footed mice, chipmunks, dogs, white-tailed deer, squirrels, horses, opossums, and raccoons.

Research surrounding Lyme Disease is sparse due to the lack of federal funding. The annual NIH investment in research is much lower than in other infectious diseases. Thirty million dollars a year is allocated to Lyme Disease research which affects over 470,000 individuals annually. However, 36 million dollars is allocated to West Nile Virus which only affects about 3,000 individuals and 202 million dollars is allocated to Malaria which only affects under 2,000 individuals. The lack of funding surrounding Lyme Disease is highly controversial and why individuals with the disease commonly suffer due to improper diagnosis and must tolerate its symptoms.

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Transmission

Ticks become infected with Borrelia burgdorferi when they have a blood meal from an infected reservoir, such as a white-footed mouse or chipmunk. When an infected tick bites an animal or human, Borrelia burgdorferi will migrate from the tick’s midgut to the salivary glands and then into the bloodstream of the new host. The spirochete then travels from the bloodstream to various tissues within the new host. The location in which Borrelia burgdorferi lands is where the most symptoms will be experienced. While no virulence factors are found within Borrelia burgdorferi, symptoms will occur as a result of the inflammatory response and damage the bacteria causes when it replicates.

Acquiring the disease depends on many factors, including, density, distribution, and prevalence of infected ticks in the individual's area. Cases of Lyme Disease are the most common in the Northeast and Northern Central states within the US. The most reported cases occur May through August due to the life cycle of ticks, tick feeding time, and increase in human activity outdoors. A tick must be attached to its new host for over 36 hours in order to transmit the disease. Adult ticks and nymph ticks can transmit the disease. However, it is much more likely to be infected by a nymph tick because of its small size and the likelihood of remaining attached for over 36 hours.

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References

Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2022, Kenyon College