Lyme disease Pathenogenisis: Difference between revisions

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[[Image:Borrelia cell outer membrane.jpeg|thumb|400px|left|This image depicts the cell membrane of <I>B. burgdorferi</I>. The membrane is very important to the microbe's ability to evade the immune system. [https://www.researchgate.net/figure/The-borrelial-cell-envelopeThis-schematic-of-the-borrelial-cell-envelope-shows-the-outer_fig4_221734507]. ]]
[[Image:Borrelia cell outer membrane.jpeg|thumb|400px|left|This image depicts the cell membrane of <I>B. burgdorferi</I>. The membrane is very important to the microbe's ability to evade the immune system. [https://www.researchgate.net/figure/The-borrelial-cell-envelopeThis-schematic-of-the-borrelial-cell-envelope-shows-the-outer_fig4_221734507]. ]]
<i>Borrelia burgdorferi</I> is a bacteria of the phylum spirochetes. It was discovered as the causative agent of Lyme disease in 1982. This bacterium has the ability to change its gene expression based on the host that it is inhabiting. For instance, the expression of proteins used in the outer and inner membranes changes from culture to tick to human host. The genome has a chromosome that is linear, and encodes more than 850 genes.<ref name=a/> The genome of this bacteria has many plasmids. Some of these plasmids are circular, and others linear.  This chromosome is very large, sizing at about one megabase (1 million nucleotides). Some <i>B. burgdorferi</i> strains have been isolated and found to have up to 20 plasmids in a given individual. Each gene has an average size of about 990 base pairs, a fairly typical size. The vast majority of the genome is coding, but there are a few non-coding segments as well. Most of the coding sequences are for “biological roles". These include genes that encode proteins meant to assist in transcription and translation, DNA replication, intra and extracellular transport, and metabolism. A decent amount of the genome is dedicated to genes involved with mobility of the microbe. Though it is known what a lot of the genome encodes for, a lot of the remaining sequences encode for unknown genes. However, they match sequences found in other organisms for the same unknown genes. Some of the genome also includes new genes, which could be good areas for research and discovery of new antibiotics.<ref name=e>Fraser, C. M., Casjens, S., Huang, W. M., Sutton, G. G., Clayton, R., Lathigra, R., White, O., Ketchum, K. A., Dodson, R., Hickey, E. K., Gwinn, M., Dougherty, B., Tomb, J. F., Fleischmann, R. D., Richardson, D., Peterson, J., Kerlavage, A. R., Quackenbush, J., Salzberg, S., Hanson, M., … Venter, J. C. (1997). “Genomic sequence of a Lyme disease spirochaete, <i>Borrelia burgdorferi</i>” Nature. December 1, 1997. https://doi.org/10.1038/37551</ref>
<i>Borrelia burgdorferi</I> is a bacteria of the phylum spirochetes. It was discovered as the causative agent of Lyme disease in 1982. This bacterium has the ability to change its gene expression based on the host that it is inhabiting. For instance, the expression of proteins used in the outer and inner membranes changes from culture to tick to human host. The genome has a chromosome that is linear, and encodes more than 850 genes.<ref name=a/> The genome of this bacteria has many plasmids. Some of these plasmids are circular, and others linear.  This chromosome is very large, sizing at about one megabase (1 million nucleotides). Some <i>B. burgdorferi</i> strains have been isolated and found to have up to 20 plasmids in a given individual. Each gene has an average size of about 990 base pairs, a fairly typical size. The vast majority of the genome is coding, but there are a few non-coding segments as well. Most of the coding sequences are for “biological roles". These include genes that encode proteins meant to assist in transcription and translation, DNA replication, intra and extracellular transport, and metabolism. A decent amount of the genome is dedicated to genes involved with mobility of the microbe. Though it is known what a lot of the genome encodes for, a lot of the remaining sequences encode for unknown genes. However, they match sequences found in other organisms for the same unknown genes. Some of the genome also includes new genes, which could be good areas for research and discovery of new antibiotics.<ref name=e>Fraser, C. M., Casjens, S., Huang, W. M., Sutton, G. G., Clayton, R., Lathigra, R., White, O., Ketchum, K. A., Dodson, R., Hickey, E. K., Gwinn, M., Dougherty, B., Tomb, J. F., Fleischmann, R. D., Richardson, D., Peterson, J., Kerlavage, A. R., Quackenbush, J., Salzberg, S., Hanson, M., … Venter, J. C. (1997). “Genomic sequence of a Lyme disease spirochaete, <i>Borrelia burgdorferi</i>” Nature. December 1, 1997. https://doi.org/10.1038/37551</ref>
The structure of the cell membrane of <i>B. burgdorferi</i> is a major contributor to the microbe’s ability to evade the immune system. It is a very unique make-up, containing many differences from a lot of other bacteria. Typically, the cell membranes of Gram-negative bacteria will be made up of lipopolysaccharides. However, <i>B. burgdorferi</i> instead uses glycolipids, which refers to a lipid linked to a monosaccharide through a glycosyl linkage.<ref name=h>”Glycolipids” LibreTexts. March 28, 2021. https://phys.libretexts.org/Courses/University_of_California_Davis/UCD%3A_Biophysics_241_-_Membrane_Biology/01%3A_Lipids/1.04%3A_Glycolipids</ref>  These glycolipids are immunoreactive, meaning that they react to the presence of certain antigens. Another important difference is related to the flagella of the cell. In a lot of cells that contain flagella, the flagella is an outer appendage that allows the cell to move. It is attached and functions through a proton motor that is located inside the membrane, but the appendage itself protrudes outside of the cell. However, in <i>B. burgdorferi</i>, there is flagella inside of the cell membrane. They exist in the space between the inner and outer cell membranes, known as the periplasmic space. These flagella are also unique in the fact that they have more functions than just allowing the cell to move. In addition to this function, they also assist in maintaining the shape of the cell. <ref name=i>Meriläinen, L., Herranen, A., Schwarzbach, A., Gilbert, L. “Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms” Microbiology. 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339653/</ref>


==Transmission==
==Transmission==

Revision as of 15:57, 15 April 2022

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Introduction

By Jp Timken

This is a photo of Borrelia burgdorferi obtained through the use of dark field microscopy. By S. Bhimji MD. [1].

Lyme disease is a vector-borne illness caused by a spirochete known as Borrelia burgdorferi. It has serious side effects and can lead to issues with the heart, brain, and spinal cord.[1] Transmission occurs through certain species of ticks, and takes several days. Removal of the tick before 36 hours can reduce chances of infection. As such, it is typically transmitted through younger, smaller ticks that can go undetected for longer periods of time.[2] The name comes from the point of discovery, which was Lyme, Connecticut in the 1970s. In spite of this, the disease is thought to have been around since the early 20th century.[3]

B. burgdorferi consists of a long body that may appear wavy or curled. The genome consists of a linear chromosome and many plasmids. The expression of these genes changes based on the host species. So, the genes expressed while in a tick will vary from those expressed after transmission to a different host organism.[3]

Lyme disease can be treated through various antibiotics. Symptoms will typically subside once treatment is administered, though they can persist in some cases. For more serious cases, intravenous antibiotics may be necessary, but if it is caught early, oral antibiotics may be prescribed by a doctor to prevent serious infection. A lot about treatment is still unknown.[4]

Borrelia burgdorferi

This image depicts the cell membrane of B. burgdorferi. The membrane is very important to the microbe's ability to evade the immune system. [2].

Borrelia burgdorferi is a bacteria of the phylum spirochetes. It was discovered as the causative agent of Lyme disease in 1982. This bacterium has the ability to change its gene expression based on the host that it is inhabiting. For instance, the expression of proteins used in the outer and inner membranes changes from culture to tick to human host. The genome has a chromosome that is linear, and encodes more than 850 genes.[3] The genome of this bacteria has many plasmids. Some of these plasmids are circular, and others linear. This chromosome is very large, sizing at about one megabase (1 million nucleotides). Some B. burgdorferi strains have been isolated and found to have up to 20 plasmids in a given individual. Each gene has an average size of about 990 base pairs, a fairly typical size. The vast majority of the genome is coding, but there are a few non-coding segments as well. Most of the coding sequences are for “biological roles". These include genes that encode proteins meant to assist in transcription and translation, DNA replication, intra and extracellular transport, and metabolism. A decent amount of the genome is dedicated to genes involved with mobility of the microbe. Though it is known what a lot of the genome encodes for, a lot of the remaining sequences encode for unknown genes. However, they match sequences found in other organisms for the same unknown genes. Some of the genome also includes new genes, which could be good areas for research and discovery of new antibiotics.[5] The structure of the cell membrane of B. burgdorferi is a major contributor to the microbe’s ability to evade the immune system. It is a very unique make-up, containing many differences from a lot of other bacteria. Typically, the cell membranes of Gram-negative bacteria will be made up of lipopolysaccharides. However, B. burgdorferi instead uses glycolipids, which refers to a lipid linked to a monosaccharide through a glycosyl linkage.[6] These glycolipids are immunoreactive, meaning that they react to the presence of certain antigens. Another important difference is related to the flagella of the cell. In a lot of cells that contain flagella, the flagella is an outer appendage that allows the cell to move. It is attached and functions through a proton motor that is located inside the membrane, but the appendage itself protrudes outside of the cell. However, in B. burgdorferi, there is flagella inside of the cell membrane. They exist in the space between the inner and outer cell membranes, known as the periplasmic space. These flagella are also unique in the fact that they have more functions than just allowing the cell to move. In addition to this function, they also assist in maintaining the shape of the cell. [7]

Transmission

Ticks that carry B. burgdorferi are able to transmit Lyme disease to many different organisms. Two types of ticks can carry and transmit the microbe, and they are both blacklegged ticks. One type, the blacklegged tick, is prevalent throughout the majority of the United States and is responsible for transmission on the Atlantic Coast, in the northeast, and in the central U.S. The other, the western blacklegged tick, is responsible for spreading the microbe throughout the western U.S. Ticks have multiple stages in their life cycle. They start as larva, then grow to nymphs, and then adults. Most transmissions are caused by nymphs, as the tick must be attached for more than 36 hours for transmission to occur. Because the nymphs are quite small compared to the adult ticks, they can be more hidden and stay attached long enough for transmission to occur. Lyme disease can’t be passed from person to person through any type of contact. For infection to occur, one must have been bitten by a tick carrying the microbe. In very rare cases, it can be passed from mother to child if an expecting mother is not undergoing any treatment but is infected.[2] When feeding, the tick passes its own saliva to the host, which is when B. burgdorferi is transmitted. When the tick first begins to feed on the host, the spirochete begins to rapidly reproduce in the gut of the tick, preparing for transmission. The tick has the ability to change the chemical composition of the saliva to damage the host immune system and response. The saliva is very important for B. burgdorferi to be transmitted from the tick to the host.[8]

Ticks are not born as carriers. To become a carrier, they too must be infected through the act of feeding on an infected host. The feeding on an infected host happens as a larva. B. burgdorferi is picked up through the feeding, and then sits in the midgut of the tick until another feeding happens. At this point, the spirochete is passed on to a new host through the saliva of the tick. This cycle is an example of an enzootic cycle, meaning that it is "existing in nature in animal reservoirs." [9] Some species can carry B. burgdorferi and not show any symptoms of Lyme disease. These organisms can then act as carriers of the spirochete. When a tick feeds on any organism like this, they can pick up the microbe and become carriers themselves until their next feeding.[3]

The symptoms of Lyme disease can vary. Often, a rash occurs shortly after transmission. The rash is circular, centering around the bite and expanding out over the course of several days. In rare cases, it may cause pain or itchiness, but it typically won’t cause any type of discomfort. In the case that a rash doesn’t appear, other beginning symptoms might take its place, such as aches, fatigue, fever, headache, or chills. These symptoms and the rash typically won’t occur together. After the initial infection period, which lasts anywhere from 3-30 days, additional symptoms may occur. The main symptom is joint and muscle pain or stiffness. Swelling of the joints can also occur, and more rashes can appear on other parts of the body. This disease can be very dangerous and cause complications with the heart, spinal cord, and even brain.[1]

Immune Response

Treatment

Lyme disease can be treated by various antibiotics. For younger children that have been infected, amoxicillin or cefuroxime can be used. Adults will most likely be prescribed doxycycline. Treatment will last for 1-2 weeks. In some more serious cases, intravenous antibiotics may be necessary. However, due to some more serious side effects, this method of treatment is only used when absolutely necessary. While some alternative methods do exist, antibiotics are the only effective treatment at this point. Additionally, even after treatment, some symptoms can persist. Unfortunately, right now there is no treatment for persisting symptoms. Treatment is most effective when the disease is caught early, so if you suspect an infection, see a doctor as soon as possible. [4]

Conclusion

References

  1. 1.0 1.1 "Signs and Symptoms of Untreated Lyme Disease" 2021. Centers for Disease Control and Prevention. https://www.cdc.gov/lyme/signs_symptoms/
  2. 2.0 2.1 "Transmission" 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/lyme/transmission/index.html]
  3. 3.0 3.1 3.2 3.3 Marques, A.R. “Lyme Disease: A Review” Current Allergy and Asthma Reports. January 8, 2010. https://link.springer.com/article/10.1007/s11882-009-0077-3
  4. 4.0 4.1 "Lyme Disease" Mayo Clinic. October 24, 2020. https://www.mayoclinic.org/diseases-conditions/lyme-disease/diagnosis-treatment/drc-20374655
  5. Fraser, C. M., Casjens, S., Huang, W. M., Sutton, G. G., Clayton, R., Lathigra, R., White, O., Ketchum, K. A., Dodson, R., Hickey, E. K., Gwinn, M., Dougherty, B., Tomb, J. F., Fleischmann, R. D., Richardson, D., Peterson, J., Kerlavage, A. R., Quackenbush, J., Salzberg, S., Hanson, M., … Venter, J. C. (1997). “Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi” Nature. December 1, 1997. https://doi.org/10.1038/37551
  6. ”Glycolipids” LibreTexts. March 28, 2021. https://phys.libretexts.org/Courses/University_of_California_Davis/UCD%3A_Biophysics_241_-_Membrane_Biology/01%3A_Lipids/1.04%3A_Glycolipids
  7. Meriläinen, L., Herranen, A., Schwarzbach, A., Gilbert, L. “Morphological and biochemical features of Borrelia burgdorferi pleomorphic forms” Microbiology. 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339653/
  8. Bockenstedt, L.K., Wooten, R.M., and Baumgarth, N. “Immune Response to Borrelia: Lessons from Lyme Disease Spirochetes” 2021.Immune Response to Borrelia: Lessons from Lyme Disease ...https://www.mdpi.com › pdf]
  9. Radolf, J.D., Caimano, M.J., Stevenson, B., Hu, L.T. “Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes.” Nature Reviews Microbiology. January 9, 2012. https://www.nature.com/articles/nrmicro2714



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