Borrelia burgdorferi sensu stricto
Borrelia burgdorferi sensu stricto
A Microbial Biorealm page on the genus Borrelia burgdorferi sensu stricto
Bacteria; Spirochaetes; Spirochaetes; Spirochaetales; Spirochaetacae; Borrelia burgdorferi; Borrelia burgdorferi sensu stricto. (1, 2)
Description and significance
Borrelia burgdorferi sensu stricto is a strain of Borrelia burgdorferi, the causative agent of Lyme borreliosis (also known as Lyme disease). The size and structure of this pathogenic spirochete (See Cell Structure, metabolism, & life cycle) allows it to easily invade tissue as well as cross the blood brain barrier, causing a multitude of negative symptoms in both the peripheral nervous system and the central nervous system of humans. As a tick-borne disease (TBD), B. burgdorferi sensu stricto is transmitted to mammals via a tick vector, which releases the bacteria into the bloodstream of its own host. (Again, see Cell Structure, metabolism, & life cycle for the full explanation.) The most common manifestations of Lyme disease are arthritis, carditis, and neurological symptoms related to the inflammatory response of the host to the invading B. burgdorferi (migraines, deficits in memory and attention, cognitive deficits, and seizures). Since its discovery in Lyme, Connecticut in 1982 by Willy Burgdorfer, Lyme disease has become the number one TBD in North America and has been the subject of much controversy and debate in the medical world. This controversy mainly revolves around the accepted treatment of Lyme disease and the possible existence of chronic Lyme disease, meaning Lyme disease not cured by the standard one-month treatment of antibiotics recommended by the Infectious Diseases Society of America (IDSA). It is likely that the cost of long-term antibiotic treatment as well as the heterogeneity of the disease symptoms and severity has led to the conflicting opinions regarding the existence of chronic Lyme. Lyme disease has caused a fundamental divide between doctors and scientists who believe it exists and those who believe it is a convenient “catch-all” diagnosis. Like the AIDS virus and the other well-known spirochete Treponema pallidum subspecies pallidum (causative agent of syphillus), B. burgdorferi represents the human fear of unpredictable pathogens and how this fear of the unknown can result in stigmatization of those with the resulting disease. (3, 4).
==Genome structure==(molecular typing article, B. burgdorferi sensu stricto is one of ten species whose genome sequences suggest they belong to the B. burgdorferi sensu lato complex. It contains a linear chromosome as well as circular plasmids. While the genome sequence of this particular strain is incomplete; the completed genomes of similar strains provide insight into the complexity of this organism. The strain B. burgdorferi B31 for example, contains a linear chromosome of 910, 725 base pairs and 17 plasmids, both linear and circular, that total approximately 533,000 base pairs. The plasmids of B. burgdorferi typically replicate in low numbers. Of these plasmids, only 71% encode functional proteins. This suggests that many of the ORFs contain “stops.” The diversity of B. burgdorferi’s plasmids provides protection from the host immune response, as they encode for 63 different membrane lipoproteins; this allows for a wide variety of combinations making the bacteria difficult to identify. B. burgdorferi contains tRNAs for all 20 amino acids but its genome seems to lack the necessary genes for their synthesis. It is capable of homologous recombination but does not have genes encoding DNA restriction enzymes. (5, 6, 7).
Cell structure, metabolism & life cycle
Cell Structure It contains seven flagella on each end, and it is the structure and location of these periplasmic flagella that allow the bacteria to be so invasive. The rotation of the filaments of the flagella within the periplasmic space causes the corkscrew-like motion characteristic of spirochetes. In other words, the bacteria is able to move forward by simply rotating in place. It also allows the bacteria to hide its flagella inside, preventing its discovery by its host's immune system. The flagella's location inside the periplasm of the cell and its complexity (it is the most complex bacterial flagella, containing both FlaA sheath proteins and FlaB core proteins) allow the bacteria to move in gel-like, liquid material (i.e. connective tissue) that prohibits the movement of most bacteria.
They are much longer than they are wide, another structural aspect which allows them to burrow through otherwise impenetrable tissue. This also prohibits observation by standard light microscopy; dark field microscopy is used instead. This focuses the light at an angle and the organism is therefore seen as a light object while the background is dark (See Figure 1).
Dark-field microscopy must be used to view spirochetes. Dark field microscopy utilizes a special condenser which directs light toward an object at a angle, rather than from the bottom. As a result, particles or cells are seen as light objects against a dark background. (1, 8, 9, 13)
Metabolism This spirochete is microaerophilic and uses glucose as its primary energy source. Like similar bacteria, Borrelia burgdorferi have limited systems of metabolism; they do not encode proteins required for the TCA cycle or for oxidative phosphorylation. They do use substrate-level phosphorylation for the production of ATP. It has been suggested that their association with ticks is due to their use of N-acetylglucosamine (NAG) for energy, as NAG is located in the chitin of tick cuticles. Despite its limited metabolic processes, B. burgdorferi can survive well in a host due to their impressive ability to avoid the host immune system. (7, 10)
Life Cycle B. burgdorferi sensu stricto, as a tick-borne disease (TBD), cycles through two main hosts: deer ticks and rodents. B. burgdorferi can live in both transmission-competent hosts and transmission incompetent hosts, providing a wide variety of host organisms. Transmission to humans is possible through tick bites, but the minimum amount of time required for transmission is not definitively known. Transmission to humans most often occurs from tick bites of the nymph life stage of the tick, meaning a young tick. Tick eggs are laid in the winter and develop first into the nymph stage and then into the adult stage during spring. This is why transmission of B. burgdorferi to new hosts occurs most often in spring. (9)
==Ecology (including pathogenesis)== 4 Spirochetes in general live in a wide variety of habitats, but mostly in host organisms. While they can inhabit the stomachs of ruminants as symbiotic bacteria, they are best known for their inhabitance of mammal hosts. B. burgdorferi sensu stricto causes the majority of Lyme disease in North America; the disease is not limited to humans but affects deer, white-footed mice, and dogs as well. While erythema migrans, better known as a "Lyme rash" used to be considered the number one symptom of Lyme disease, it is now know that Lyme disease affects multiple systems most likely due to the inflammation that the bacteria causes. While its multiple "stealth" systems prevent its destruction by its host cell, it does trigger an intense immune response and therefore inflammation. The bacterial ligands DBPA/B, p66, BBk32 and OspC, which allow the bacteria to invade the joints and the heart, have been identified on B. burgdorferi and are likely the main contributor to inflammatory response by host immune cells. Current research also suggests that B. burgdorferi activates the release of dissemination molecules by the host which allow the bacteria to easily enter tissues. Strangely, it does not contain many virulence factors and therefore must rely on its crafty invasion of the host. Lyme disease is characterized by its wide variety of manifestations. Borrelia burgdorferi are able to alter the expression of their genes in response to their host environment, thereby creating a unique phenotype that best survives the host environment and therefore a unique set of symptoms. Symptoms range from resemblance to MS, to rheumatoid arthritis, to neurological disorders, to simple migraines and surface skin reactions. Fatigue, lack of attention, "brain fog" resulting from decreased blood flow, neuropathy, and facial palsy are also common symptoms. It is easy to understand why Lyme disease is called the "Great Imitator." B. burgdorferi sensu stricto most often causes neurological symptoms, as described in the "Interesting Feature" section. Much more research is needed to determine both how B. burgdorferi responds to the host immune response and why it is so resistant to antibiotic treatment. In most animal models, B. burgdorferi is resistant to antibiotic treatment yet the common treatment of Lyme disease is still a single round of antibiotics. As previously stated, the ability of the bacteria to enter dense tissue may mediate this antibiotic resistance, as the antibiotics simply cannot reach the bacteria. A current animal model in mice also found that the bacteria are able to attach themselves to collagen tissue, which prevents their removal by host immune cells. Lastly, the ability of the bacteria to alter its own gene expression in response to its environment allows it to alter its antigen expression, effectively confusing the host's immune response cells. The death of the bacteria within the host is also damaging, as it induces a Jarish-Herxheimer response. This suggests that dying bacteria release damaging toxins, which further weaken the immune response allowing surviving cells to thrive. It is likely that long-term infection (chronic Lyme disease) is more of an auto-immune disorder, resulting from the overstimulation of the immune response. This process is similar to diseases like Alzheimer's, in which the immune response is ultimately more damaging to the host due to its overextension. (4, 11)
==Interesting feature== 12 In addition to the supreme control over its own gene expression, an interesting feature of Borrelia burgdorferi sensu stricto is the variability within the strain of a certain surface protein, OspC. These surface proteins seem to differ in expression based on their environment; one type is common to strains isolated from ticks but uncommon in strains isolated from humans, one is commonly seen in bacteria causing local infections, and one is common in bacteria causing multi-systemic manifestations of the disease. Overall, there are 19 major OspC groups and at least 13 alleles exist in even small populations of B. burgdorferi sensu stricto. A recent study found that bacteria expressing OspC groups A, B, I, and K were most likely to cause systemic disease in humans, including neuroborreliosis, or neurologic Lyme. This research solidifies B. burgdorferi sensu stricto's unique ability to alter its phenotype based on its host environment, as the expression of these surface proteins can be altered. It also suggests that Lyme disease may need to be delineated into different categories based on the surface proteins that the specific invader bacteria expresses. (12)
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