Megan Eifert 

Background

The helical shaped pathogen Borrelia burgdorferi is a member of spirochete bacterium that is best known as the causative agent of Lyme disease. Belonging to the phylum Spirochaetes, these bacteria are characterized by a lipid bilayer known as the outer membrane sheath, as well as an inner space between a long cylindrical protoplasm and outer membrane sheath referred to as the periplasm (Metapathogen, 2012). Genus Borrelia comes from the French bacteriologist Amedee Borrel who identified a set of organisms that caused “tick-borne and louse-borne relapsing fever in humans and animals” (Metapathogen, 2012). Specific to the group Borrelia burgdorferi typically only 1 μm wide but up to 25 μm long, a unique characteristic of wavelike bodies and flagella are bound between the inner and other cell membranes, proving to be vital in the success of these bacteria. This feature is especially important to defining the highly invasive classification of these bacteria by allowing the pathogen to travel effectively through tissue of its infected host (Burke, 2005). Similarly an important feature of B. burgdorferi are their outer surface proteins that have been researched to play a large role in the transmission of the pathogen as well as been the focus of those working on producing an effective vaccine against it (Burke, 2005).

Metabolic capabilities are limited in these bacteria and therefore gaining energy is a task relied upon the hosts in which B. burgdorferi infect. With an optimal growth condition at 32° C in a low oxygen environment, even the best conditions demonstrate a slow generation time of between 12 to 24 hours (Tilly, 2008). Using glucose and carbohydrates as their main energy source, their genome has been identified to encode transport proteins such as ABC transporters and enzymes that are utilized in the phosphotransferase system and others similar that have the ability to gather compounds from both host or environment (Burke, 2005). Without the capability to produce energy from the TCA cycle, oxidative phosphorylation or an electron transport train, B. burgdorferi utilizes substrate-level phosphorylation to produce ATP within the cell necessary for these bacteria to remain successful (Rosa, 2005).

There are three species of B. burgdorferi that have been identified in causing most cases of human disease. With a natural reservoir found to be a variety of small mammals, B. burgdorferi sensu stricto, B. garinii, and B. afzelii are the typical strains identified in almost all cases of clinical disease. Specific to the United States, B. burgdorferi sensu stricto is the only species clinically associated with human disease whereas all three species have been found in Europe, and B. garinii and B. afzelii have both been identified in Asia (Metapathogen, 2012).

Clinical Significance

Although infection within natural hosts does not regularly cause disease, Borrelia burgdorferi is a tick-borne obligate pathogen that when infection occurs in humans can elicit the human immune-patholgical response and cause Lyme disease (Borrelia, 2007). Dr. Alan Steere and his team first clinically identified Lyme disease in 1977 as an infectious illness that continues to be the leading vector-borne disease in the United States (Borrelia, 2007). Through research of geographic regions with a surge of patients exhibiting seasonal occurrence of similar symptoms, Dr. Steere hypothesized the epidemiology of Lyme disease suggested transmission of the pathogen was occurring through an arthropod vector. Following the lead of Dr. Steere, a Dr. Willy Burgdorfer began to study a group of spirochetes found and collected from midgut tissues of ticks native to areas relative to the Lyme disease outbreaks. The bacteria isolated continuously produced a skin rash similar to erythema migrans when tested on rabbits within a laboratory setting and samples from Lyme disease patients reacted with the bacteria when used in indirect immunofluorescence assays (WI, 2011). As a consequence of these observations, this set of organisms was first given their now recognizable name, Borrelia burgdorferi.

Clinical manifestations of Lyme disease vary upon the species identified as the causative agent however; many common symptoms and features are shared across all cases of disease. According to reports from Mayo Clinic, most often the first symptoms described include an erythema migrans rash often in the shape of a bulls-eye at the site of the bite, accompanied by symptoms that most resemble an influenza-like infection (Lyme, 2015). Once patients exhibit these skin lesions, non-specific symptoms such as “headaches, generalized lymphadenopathy, generalized lymphadenopathy and splenomegaly, migratory musculoskeletal pain, hepatitis, sore throat, non-productive cough, conjunctivitis or periorbital edema” may arise, causing in most cases the discomfort associated with a diagnosis of Lyme disease (Lyme, 2015). Specific to most cases identified in the United States by the B. burgdorferi, arthritis is one of the main associated symptoms that patients struggle with.

When infection persists to stage 2 after a few weeks, Mayo Clinic sources indicate about 15% of patients develop neurological deficits and abnormalities such as “meningitis, encephalitis, cranial neuritis (including bilateral facial palsy), motor or sensory radiculoneuritis, mononeuritis multiplex, or myelitis” (Lyme, 2015). Once neurological problems begin, patients can develop cardiac complications as well while continuing to experience a high amount of musculoskeletal pains throughout the body. When symptoms of Lyme disease persist beyond the typical treatment time, chronic Lyme disease can set in and patients experience post-treatment Lyme disease syndrome resulting from weakened immunity, systemic bacterial infection and inhibited cellular function and protection (Transmission, 2015). Over two-thirds of patients diagnosed with Lyme disease by infection of B. burgdorferi will develop chronic neurologic or skin involvement and non-specific arthritis. Symptoms characteristic of chronic fatigue syndrome have been described as lasting for years following infection, proving infection with this bacterium can live in harmony within its human host making it a successful pathogen. According to the CDC, Lyme disease affects approximately 60,000 people worldwide per year however; mortality caused by the pathogen remains low at only 114 deaths reported from the disease in the United States between 1999-2003 (Transmission, 2015). Lyme disease can be accompanied by a wide variety of systemic involvement with varying clinical manifestations dependent on the stage of disease identified making both the course of illness and treatment inconsistent between patients.

Borrelia burgdorferi elicits a variety of strategies in order to penetrate the immune systems of its hosts in hopes to successfully remain a viable bacterium. Inducing both the innate and adaptive immune responses, the bacteria have adapted to their reservoir hosts causing ineffectiveness of immunity to clear the bacteria out of the system entirely. Prior to activation, cleaved complement molecules form on the surface of the bacteria to help promote bacteriolysis while negatively regulating the complement system through various regulators to avoid host tissue damage (Tilly, 2008). With the goal of inhibiting the complement system, B. burgdorferi utilize outer surface proteins hosted on their outer membranes to bind complement regulators in order to successfully inhibit the complement system and its killing response. With the complement system inhibited, the bacteria are able to better survive within the blood stream and thus promoting further disease manifestations (Tilly, 2008).

Vaccination for Lyme disease is a concept of both the publics’ past and future but not present. Administered in three doses, the first and only of its kind a vaccine against Lyme disease was licensed in 1998 by SmithKline Beecham (Poland, 2011). The vaccine in theory was to stimulate antibodies that would attack B. burgdorferi within the vectors gut as it fed on its human host, thus preventing the bacteria to enter the body and showed to be 78% effective following all doses completion (Poland, 2011). In 2002 the company producing the vaccine had removed it from the market and ever since a similar vaccine to protect humans against Lyme disease has not been re-introduced to the public.

Diagnostic and Treatment

Diagnosis of Lyme disease can be difficult due to the various nonspecific signs and symptoms associated with not only infection by Borrelia burgdorferi, but characteristic of many similar diseases. Typically the rash characteristic of Lyme disease in an area known to host ticks that transmit the disease does not warrant further testing for a diagnosis. Most often used to provide a more definitive Lyme disease diagnosis is the use of an enzyme-linked immunosorbent assay test. ELISA detects Lyme disease by identifying antibodies to its causative pathogen, although this test may provide false-positives or negatives even when the bacteria is present due to the stage the disease is in (Borrelia, 2007). If an ELISA test proves positive, Western blot tests are used to confirm infection of B. burgdorferi, which identify antibodies against multiple proteins characteristic of the pathogen (Lyme, 2015).

Several therapeutics are used to treat patients infected with Lyme disease and as with most disease treatments the sooner treatment is able to begin, the better and sooner recovery is achievable. Oral antibiotics are used as the first line of standard treatment with an early-stage diagnosis of Lyme disease. With a 14 to 21 day regimen, antibiotics prescribed according to Mayo Clinic typically include doxycycline for adults and children older than 8, or amoxicillin or cefuroxime for adults, younger children, and pregnant or breast-feeding women (Lyme, 2015). Oral antibiotics are used most often to treat skin rashes and influenza-like symptoms associated with the first stages of Lyme disease. Intravenous antibiotics may be employed for treatment if the disease has involved the central nervous system and this method of treatment has been shown to be effective in eliminating the infection but not without lingering symptoms according to the CDC. When chronic Lyme disease or post treatment Lyme disease syndrome is suspected, antibiotics are not effective in treating symptoms or the disease, and effective treatments remain unknown once the disease has progressed on. Although much research is unavailable, many living with chronic Lyme disease explain turning to natural remedies as treatment such as dietary suggestions to help increase immune function or adding supplements to help improve cell structure and function to help alleviate symptoms (Borrelia, 2007).

References

Borrelia burgdorferi. (2007). Retrieved March 25, 2017, from http://www.lymeneteurope.org/info/borrelia-burgdorferi

Burke G, Wikel SK, Spielman A, Telford SR, McKay K, Krause PJ, et al. “Hypersensitivity to Ticks and Lyme Disease Risk.” Emerging Infectious Disease. 2005 Jan. Volume 11(1), p. 36-41.

Lyme disease. (2015). Retrieved March 25, 2017, from http://www.mayoclinic.org/diseases-conditions/lyme- disease/basics/definition/CON-20019701

MetaPathogen.com/Borrelia burgdorferi. (2012). Retrieved March 25, 2017, from http://www.metapathogen.com/borrelia/

Poland GA. Vaccines against Lyme Disease: what happened and what lessons can we learn? Clin Infect Dis. (2011) 52 (suppl 3): s253-s258. Retrieved March 25,2017.

Rosa, PA., Tilly, K., and Steward, PE. “The Burgeoning Molecular Genetics of the Lyme Disease Spirochaete.” Nature Reviews Microbiology. 2005. Volume 3(2), p. 129- 143.

Tilly, K., Rosa, P. A., & Stewart, P. E. (2008, June). Biology of Infection with Borrelia burgdorferi. Retrieved March 25, 2017, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/

Transmission. (2015, March 04). Retrieved March 25, 2017, from https://www.cdc.gov/lyme/transmission/

WI, K. T. (2011, May). Lyme Disease. Retrieved March 25, 2017, from http://textbookofbacteriology.net/Lyme.html