Borrelia burgdorferi NEU2011
Borrelia burgforferi NEU2011
A Microbial Biorealm page on the genus Borrelia burgdorferi NEU2011
Higher order taxa
Species- Borellia burgdorferi
Description and Significance
Borellia burgdorferi is a spirochete, which are cells that are both gram-negative and spiral-shaped with endoflagellum. The flagella at both ends rotates in opposite directions which allows the bacterium to penetrate through different tissue layers (see Figure 1) (4). B. burgdorferi also is characterize by a slow generation time, at around 12-24 hours and it can be cultured in the lab on Barbour-Stoenner-Kelly (BSK) medium, which includes rabbit serum (6).
The study of Borellia burgdorferi is very significant because it is the tick-borne agent of Lyme disease. Lyme disease is carried out by the bacterium, and transmitted through a variety of deer ticks, including Ixodes dammini (2). The disease was first discovered in 1982, by Willy Burgdorfer. He isolated spirochetes from the mid guts of Ixodes ticks and demonstrated that spirochetes and the immune serum reacted together from patients who were diagnosed with Lyme disease. Symptoms of the disease consist of inflammation all around the body, arthritis, heart problems and it can also affect the nervous system (8). Researchers have been studying Lyme disease for a decade after they discovered the complete genome sequence for B. burgdorferi strain 31. Recently researchers determined the whole genome sequences of thirteen isolates of B. burgdorferi. The significance of this discovery proves that researchers will be able to improve on the understanding of its pathogenesis, and provide prevention strategies in the near future (7).
The Borrelia burgdorferi genome contains 1.44 Mega base pairs with the number of G+C bases totaling 28%. It has a total of 22 DNA molecules including 21 extrachromosomal DNA elements, the largest known number of any bacterium (1). These include 12 linear and 9 circular plasmids which range from 5 to 56 kilobases (3). The plasmids contain a total of 1706 genes, including many pseudogenes, which suggests that the genome is actively evolving. It is also one of the few known bacteria to have a linear chromosome. Studies have shown that the linear plasmids have covalently closed ends, which occurs in some animal viruses but has not been found in prokaryotic organisms (5). Figure 2 illustrates the total genome of a sequenced strain of Borrelia burgdorferi.
Cell Structure and Metabolism
The cell consists of a protoplasmic cylinder that includes the genome and cytoplasmic membrane, all enclosed by a flexible multilayered envelope. The cells have 5-7 coils and contain anywhere from 7-20 endoflagella, that are embedded in the periplasm and are located at each pole (4) (see figure 3). The machinery used in motility is similar to other bacteria in that it has a filament, hook and basal body (6).
B. burgdorferi is classified as a microaerophilic chemoorganotroph; they derive energy from metabolizing organic molecules and require oxygen to survive, but in very low concentrations. They are known to have very limited metabolic capacity and are therefore difficult to culture in the lab (6).
The white-footed mouse, Peromyscus leucopus, is proposed to be the principle carrier of Borrelia burgdorferi. However, it is also seen in other small mammals and birds. Ticks acquire the bacteria by feeding on the blood of infected mammals and birds. Subsequently, they act as a reservoir and can also transmit it to other animals they feed upon, including humans. (6)
Throughout the world there are the variety of species of ticks that act as vectors for B. burgdorferi. In Northeastern America, the bacterium resides in a species of tick called Ixodes scapularis, in the Pacific northwest of North America the bacterium live in the gut of Ixodes pacificus, in northern Asia they thrive in Ixodes persulcatus, and throughout Europe the bacterium resides in the species Ixodes ricinus. However, other species of ticks have not been shown to be a reservoir for B. burgdorferi (6). There is a broad spectrum of hosts that B. burgdorferi can be transmitted into. (2) Once transmitted, B. burgdorferi can reside and take on pathogenic effects in a variety of vertebrates which include rodents, rabbits, some species of birds, deer and even a few species of reptiles. (6)
Borrelia burgdorferi is very pathogenic and is the cause of Lyme disease.B. burgdorferi is incorporated into the body through the bite of the tick. When a human is initially bitten by a B. burgdorferi carrying tick, the area around the bite contracts a skin disorder known as erythema migrans (see Figure 4), and this creates a red ring, which looks a bullseye around the bite site. The saliva from the tick contains many different substances that can effect the immune system response at the bite site, which in turn helps the bacteria to more readily pass into the circulatory system (6). From the circulatory system B. burgdorferi can spread to the heart, liver, joints, ect. This is what causes the wide array of pathogenic effects and why each specific case of Lyme disease varies (15). However, B. burgdorferi does not cause pathogenic affects is all animals, some such as deer, can get infected but not show any symptoms of a disease (9). Therefore, not only does the specific carrying vector of the bacterium vary from region to region, the pathogenic effects differ as well.
There are three different stages in Lyme disease; primary, early disseminated and chronic (15). After being infected with B. burgdorferi the symptoms of the Lyme disease, headache, aches, chills and fever can manifest themselves. Some of the first symptoms of Lyme disease are very similar to many other common diseases, including the flu and common cold. Therefore, the disease can be hard to diagnose and can progress into the later stages, which are characterize by arthritis, inflammation and on rare occasion neurological or psychological symptoms(15). In stage three of the diseases, B. burgdorferi can cross the blood brain barrier and can cause significant neural damage. The process of the bacterium crossing the blood brain barrier is not yet fully understood (16). In order to reduce the risk of contracting Lyme disease one should wear long sleeves when walking through long grass or brush, especially during the summer months. Ticks can not hop or move quickly, normally they just wait for a host to pass by them before dropping (2). If infected the treatment includes various antibiotics, but it needs to be caught early enough. Even with proper antibiotic treatment, the disease can relapse and chronic symptoms can persist (15).
“The bba64 gene of Borrelia burgdorferi, the Lyme disease agent, is critical for mammalian infection via tick bite transmission” (10)
Gilmore et al. (2010) has demonstrated that the bba64 gene is vital in the transmission of B. burgdorferi from ticks to mammals. In order to illustrate this, the researchers created a B. burgdorferi mutant strain that can not synthesize the bba64 gene product. This strain was proven to be infectious to mice when it is directly injected into the tissues of the mouse, yet it could not be passed from an infected tick to the mouse. Furthermore, larval ticks that fed on infected mice were shown to have the mutant strain of the bacteria. Therefore, the strain is clearly infectious; however, bba64 is needed in order to pass the bacteria from tick to host (10). Further research needs to be done in order to fully understand the mechanisms involved in transmitting B. burgdorferi.
"A Chromosomally Encoded Virulence Factor Protects the Lyme Disease Pathogen against Host-Adaptive Immunity" (14)
One of the reasons why B. burgdorferi is very pathogenic is due to its ability to evade the host's immune system. The exact mechanisms are still unknown. However, a recent study done by Yang et al. (2009) demonstrates that the bacteria expresses genes in vivo, which express surface-located membrane protein 1 (lmp1). When lmp1 is expressed it helps to elude the hosts immune response and could help to generate the chronic infection that is associated with the disease. The researchers examined mice infected with the bacteria and found that lmp1 is expressed in extremely high levels during the early stages of the disease. At this point, the immune system response to the bacteria would be greater. Additionally, deleting lmp1 made it more difficult for B. burgdorferi to survive in the host and for it to produce symptoms of the disease in the mice. This was further validated by reinstating lmp1, which then induced symptoms of the disease in the mice. (14) This helps to demonstrate the importance of lmp1 as a virulence factor that helps to protect B. burgdorferi from the host's immune system.
A recent article published in the journal Medical Hypothesis proposes that there is a link between autism and Lyme disease. This hypothesis is still in the early stages of development and much more actual research needs to be done on the mechanisms and processes involved. Bransfield et al. proposed this link based on epidemiological findings, individual case studies, similarities between symptoms in both diseases and a variety of lab tests, including testing autism patients for B. burgdorferi (11). This article also makes a point that Lyme disease could be one of many environmental factors that might contribute to the onset of autism.
1. Casjens, S., Palmer, N., Van Vugt, R., Mun Huang, W., Stevenson, B., Rosa, P., Lathigra, R., Sutton, G., Peterson, J., Dodson, R. J., Haft, D., Hickey, E., Gwinn, M., White, O. and M. Fraser, C. (2000), "A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi." Molecular Microbiology, 35: 490–516. doi: 10.1046/j.1365-2958.2000.01698.x
2. Meyerhoff, John O. 2009. "Lyme Disease Causes and Transmission." E-Medicine from WebMD, New York, NY: Healthwise Publishing.
3. Norris, Steven J. 2006. "The dynamic proteome of Lyme disease Borrelia." Genome Biology, 7:209 doi:10.1186/gb-2006-7-3-209.
4. Madigan MT, Martinko JM, Dunlap PV, Clark DP. 2009. Brock Biology of Microorganisms. Twelfth Edition. San Francisco, CA: Pearson/Benjamin Cummings.
5. Barbour AG, Garon CF. July 1987. "Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends." Science Magazine, Vol. 237 no. 4813 pp. 409-411 DOI: 10.1126/science.3603026
6. Kahl O, Lane RS, Stanek G. 2002. Lyme Borreliosis : Biology, Epidemiology and Control. New York, NY: CABI Publishing.
7. Schutzer SE. 2011. "Whole genome sequences of Borellia Burgdorferi". Journal of Bacteriology. 4:193 doi:10.1128/JB.01158-10.
8. Sternbach G, Dibble CL. 1996. "Willy Burgdorfer: Lyme Disease". Journal of Emergency Medicine. 4:631
9. Wormser GP, Dattwyler RJ, Shapiro ED, et al. "The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America." Clin Infect Dis. 2006;43(9):1089-1134
10. Gilmore Jr, Richard D et al. "The bba64 gene of Borrelia burgdorferi, the Lyme disease agent, is critical for mammalian infection via tick bite transmission." Proceedings of the National Academy of Sciences of the United States of America, 2010: (107): 7515-7520.
11. Bransfield, Robert C. et al. "The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders." Medical Hypotheses, 2007: 967-974.
14. Yang X, Coleman AS, Anguita J, Pal U, 2009 "A Chromosomally Encoded Virulence Factor Protects the Lyme Disease Pathogen against Host-Adaptive Immunity." PLoS Pathog 5(3): e1000326. doi:10.1371/journal.ppat.1000326
15. Lyme Disease. (2010, February 23). Retrieved from PubMed Health: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002296/
16. Grab, D. J., G. Perides, J. S. et al 2005. "Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier." Infect. Immun. 73:1014-1022.
Edited by Agnes Chojnowska, Austin Purdy, Aman Kaur and Tan Pham for BIOL2321 Microbiology, 2011, Northeastern University