What is Lyme disease?
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).