What is Lyme disease?
History
In 1982, Dr. Burgdorfer and his team of scientists where the first to discover the previously unknown spirochetal bacterium, called Borrelia burgdorferi, in a tick species, known as Ixodes scapularis (Burdgorfer 1982). This spirochete, which is a spiral shaped bacteria, was later found in patients with early Lyme disease and patients’ immune responses were linked with the bacterium, proving it was the cause of disease (Steere et al. 2004). Since this time, there has been a lot of research conducted regarding how Borrelia burgdorferi infects humans and how it causes disease symptoms.
Transmission of Disease
Lyme disease, also known as Lyme borreliosis, is a bacterial infection one can get from the bite of an infected tick (deer tick). This tick spreads the disease in the northeastern, mid-Atlantic, and north-central United States. Ticks are able to attach to any part of the human body where it may bite and transmit the Lyme disease bacterium to the human host after about 36-48 hours. Most humans are infected by ticks in their nymphal stage, a stage where they are very small (less than 2 millimeters), making them extremely difficult to see or detect. Adult ticks can also transmit Lyme disease bacteria, but because they are larger than nymphs they are more likely to be discovered and removed before they can transmit the disease (CDC Lyme disease transmission).
Biology of B. burgdorferi
The Lyme disease agent contains nine circular and 12 linear plasmids, which are small pieces of DNA, that make up about 40% of its DNA (Casjens 2000). Some of the plasmids are thought to be extremely important to the survival of the bacteria and can be thought of as small chromosomes. Most of the bacterial DNA codes for lipoproteins, including many outer-surface proteins, which are proteins found in the inner and outer regions of the cytoplasmic membrane of a cell. One outer membrane lipoprotein, called VlsE, undergoes antigenic variation, meaning it changes its shape often, which is a crucial function needed to bypass the immune system of the human host (Bankhead 2007). In order for the bacteria to survive in the tick and then infect and survive in a human or other mammalian host, it expresses certain proteins at specific times during its life cycle. For instance, the bacterium expresses OspA when surviving in a dormant state in the midgut of a tick. In order to infect a mammalian host, the bacterium downregulates OspA and upregulates OspC. B. burgdorferi is not known to produce any toxins and instead causes infection by migration through tissues, adhesion to host cells, and evasion of the immune system (Steere et al. 2004).
Symptoms of Lyme disease and Treatment
Within about 3-32 days of infection, a slowly expanding skin lesion, called erythema migrans (EM), forms at the site of the tick bite in about 70-80% of cases of Lyme disease. This skin lesion is often accompanied with flu-like symptoms, such as fatigue, headache, fever, and by signs that suggest dissemination of the spirochete. The body first responds to infection through the innate immune response by sending macrophages to engulf and kill the bacteria. At the site of the lesion, inflammatory cells produce pro inflammatory cytokines, which are small proteins that promote inflammation at the scene of infection. A couple of days after infection, most patients have an IgM antibody response to one of the outer-membrane proteins of the bacteria, which fights against the infection. After having been infected for a few weeks, if the bacteria have not been killed off by the body’s own immune system or prescribed antibiotics, it will often spread throughout the body by means of blood and other fluid transport (Steere et al. 2004).
In order to disseminate, the bacteria often bind to extracellular proteins on host cells or tissue matrices. Despite the immune system being very active during dissemination, B. burgdorferi may survive by changing antigenic expression of surface proteins and inhibiting certain host immune responses (Steere et al. 2004). A change in antigenic expression is basically a change in outer membrane protein shape or form. This makes it difficult for the body to recognize the bacteria and fight against it because its identifier is always changing. The protein that is essential for this immune system evasion is the VlsE lipoprotein, which undergoes these antigenic variations (Norris 2006). Most of the time with the body’s own defenses in combination with antibiotic treatment, the disease is cured. However, if left untreated patients will have a persistent infection, which often results in arthritis, due to inflammatory responses in joints. Other long lasting symptoms include heart conditions and neurological problems too (Steere et al. 2004).
Most often, Lyme disease patients are treated with doxycycline and other antibiotics. Some antibiotics used recognize an invariable region (a region that does not change shape) of the VlsE protein and therefore will recognize the disease that way. Patients with chronic arthritis, who test negative for Lyme disease after 2 months of antibiotics after having Lyme disease, are treated with anti-inflammatory agents, often due to inflammation in the joints (Steere et al. 2004).
So, you know Dom, that I will be keeping a close eye on your project since it is about Lyme Disease. Great opening overview.
A suggestion to add on might be to look into the fact that Lyme is considered an “emerging infectious disease”, which is why the Edwards lab is so interested in looking into the disease. Very much like how we’ve been talking about the papers that we’ve read in class all semester, maybe adding this component would add to the impact of your website and why people should care.
Also, more specifically, there is great information on how the immune system removes the pathogen from the body. However, what does this spirochete target specifically when it evades the immune response and what changes does it cause?
Thank you, Kat, for your feedback. I have included much more information about the emergence of the disease in the history and metabolic context page. Also, the bacteria doesn’t really target anything specific. It just moves throughout the tissues in the body and basically binds to the extracellular matrix of the host cells. The bodies own immune system tends to do all the damage.
I thought this review was very informational and I have a better understanding of the disease after reading this review. My question surrounds the VIsE lipoprotein and antibiotics that are supposed to target it to stop the Lyme infection. How does this work and what is meant by the “invariable region?”
The VlsE lipoprotein contains certain areas that are subject to change and other areas that are not, these are the invariable regions. Antibodies will more easily recognize the region that does not change.
This summary covers a lot of topics that were presented in a manner that someone unfamiliar with this material, such as myself, could follow easily. The amount of citations to support your information is good. My only criticism is compositional in nature; I personally would have put the “History” section before the “Transmission of Disease” section.
Thank you very much, Max.
Great start. I love the subheadings. Hadn’t thought of that for my own title page but it’s a great idea and makes the navigation much easier. I agree with Max, I think history, or something to that effect, should go first, or perhaps a fusion of the two sections. I also wonder if you should add nymphs or nymphal stage to the biochem primer. You talk about it briefly, but it could be helpful in case people are more curious about the stage a tick might be at when they get bitten.
Another suggestion is in the history section, the organismal names and jargon got a little heavy. If I were a non-scientist I think it would deter me from reading that section.
Otherwise it’s well-organized and solid. I liked the figures too.
Ed, I thought about adding nymphs to the primer page, but I thought that it might not be enough of a biochemical term. I would like to keep the little blurb about the history just to give people some context about how recent the discovery is because it seems like Lyme disease has been around forever.
Very well organized display of information. It was clear and gave a very good overview on the transmitting of Lyme disease. A question I have is can it be cured if the patient has not reacted timely to a bite?
It can be cured, especially with antibiotic treatment. The earlier the better. There is not really a set length of time in which one must be treated. Most people will be cured with antibiotics at any point of the disease development though the risk of still being infected even after treatment increases with time. So, the faster it is treated, the better.
I live in an area that is inhabited by many deer and an overabundance of deer ticks. Lyme disease is a serious health issue and I was aware of much of your content just from being a concerned parent. Your write-up went beyond my layman’s knowledge and provided the “whole story”. It is interesting to know the chameleon like tendencies that the bacteria employs to escape detection. Aside from a misspelled word in your first “History” paragraph and a missing verb in your penultimate paragraph, the write-up is well done and very informative.
Thank you very, Jan. I will try to make those corrections.
This was a very comprehensive and clear summary on a disease that remains persistent and detrimental in the Northeast and certainly the heavily wooded area that I grew up in. The biggest Lyme issue that really faced my town was that dogs were on multiple occasions becoming inflicted with Lyme without it being noticed for long periods of time. It is obviously more difficult to pick up on ticks attached to animals with more substantial fur coats, which makes me wonder the easiest way to pick up on the symptoms in the scenario where the animal as opposed to the human becomes inflicted in order to catch the disease earlier on.
Unfortunately, I don’t really know how to detect if a dog has Lyme disease or not. I’m not sure if they form rashes or even similar symptoms to humans.