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<blockquote><i>Borrelia burgdorferi </i> is the main bacterium that is responsible for [http://en.wikipedia.org/wiki/Lyme_disease Lyme disease], a tick-borne infectious disease. Since the late 1800s and early 1900s, cases of undefined infections were reported throughout Europe that would now be categorized as cases of Lyme disease <sup> [http://www.austincc.edu/microbio/2704x/bb.htm] </sup>. However, it was not until the 1970s when Lyme disease became of interest to scientists. In Lyme, Connecticut, and its surrounding areas, there were reports of peculiar cases of arthritis during the 1970s.  Because the cases were mostly children who played in wooded areas, especially during the summer months, researchers quickly found the correlation between Lyme disease and ticks. It wasn’t until the 1980s when researchers found the bacteria in ticks that were responsible for the infection. The bacterium was later named <i>B. burgdorferi </i> in respect to Willy Burdorfer, one of the researchers credited to its discovery <sup> [http://www.niaid.nih.gov/topics/lymedisease/understanding/Pages/intro.aspx]</sup>. Now, Lyme disease is the most prevalent tick-borne illnesses present in the Western Hemisphere <sup>[http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/205_212.Rupprecht.00091.PDF]</sup>. Ticks infected with <i>B. burgdorferi </i> transmit the bacteria to the host organism where the bacteria then adapt to the organism’s immune system and environment in order to grow and divide. With <i>B. burgdorferi </i>'s painless and almost unnoticeable transmission until after the spread of the bacteria and the bacteria's adaptive mechanisms, diagnosis of Lyme disease is often delayed. Because of <i>B. burgdorferi </i>’s effective survival strategies within a host, the lack of a working and available vaccine, and symptoms characteristic of other illnesses, Lyme disease is becoming a widespread public health concern. </blockquote>

==<b>Manifestations of Infection in Humans</b>==
===Epidemiology===
====United States====
[[Image:Lyme_Disease_Risk_Map.gif |thumb|350px|right| Figure 1. The risk areas of contracting Lyme disease in the United States. By The Center for Disease Control and Prevention (website) [Public domain], via Wikimedia Commons.[https://upload.wikimedia.org/wikipedia/commons/9/9d/Lyme_Disease_Risk_Map.gif]]]
There were 19,931 human reported cases of Lyme disease in the United States in 2006 <sup> [http://www.antimicrobe.org/new/b84.asp] </sup>. Reports of Lyme disease are more common in areas that have high populations of ticks. Ixodes, a species of ticks, and in particular [http://en.wikipedia.org/wiki/Ixodes_scapularis Ixodes scapularis] (the deer tick), are known to be the predominant couriers of Lyme disease in the United States. Within the United States, these ticks and therefore Lyme disease are generally most found in the Northeastern region, the Northwestern regions, and the Northcentral regions of the United States (Figure 1). Ticks are most active in the warmer seasons of the year <sup> [https://naturalmedicines.therapeuticresearch.com/databases/medical-conditions/l/lyme-disease.aspx] </sup>. Being outdoors, especially in wet and wooded areas increases risk of contact with ticks, as they prefer damp environments. <br>

====Worldwide====
Cases of Lyme disease are found worldwide, but tend to be concentrated in certain temperate regions. Lyme disease is found most commonly in the Czech Republic, Germany, Finland, Estonia, Belgium, France, Slovakia, Hungary, Poland, Britain, Norway, and Scotland in Europe, British Columbia and Ontario in Canada, and the United States <sup> [http://lymepeople.com/lyme-disease-is-found-worldwide/] </sup>. <i>B. burgdorferi </i> is characteristic to the United States, and different species of <i> Borrelia </i> , such as [http://en.wikipedia.org/wiki/Borrelia_afzelii <i> B. afzelli </i>], [https://microbewiki.kenyon.edu/index.php/Borrelia_garinii <i>B. garinii</i>], and [http://en.wikipedia.org/wiki/Borrelia_spielmanii <i>B. spielmanii</i>], are responsible for Lyme disease in other places of the world <sup> [http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/205_212.Rupprecht.00091.PDF] </sup>.

<br> <br>

===Symptoms===
<br>
<i> B. burgdorferi </i> attaches to the host organism through the site of a <i>Borrelia burgdorferi</i> -infected tick bite and travels through the bloodstream. At the initial tick bite site, [http://en.wikipedia.org/wiki/Erythema_chronicum_migrans erythema migrans], a circular skin rash (Figure 2), usually appears within a month and can increase in size over time <sup> [http://www.sciencedirect.com/science/article/pii/S1286457904000097] </sup>. This stage of infection is called the early localized stage and is often accompanied by flu-like symptoms such as fatigue, body aches and fever <sup> [http://www.niaid.nih.gov/topics/lymedisease/understanding/Pages/intro.aspx] </sup>. The following stage, the early-disseminated stage, is characterized by symptoms of further infection. <i> B. burgdorferi </i> targets various body tissues such as the skin, motor joints, the nervous system, and the cardiac system leading to symptoms like body aches and persistent skin rashes <sup> [https://naturalmedicines.therapeuticresearch.com/databases/medical-conditions/l/lyme-disease.aspx] </sup>. For infected individuals that did not have the initial skin rash, these secondary symptoms are usually the first sign of infection and Lyme disease <sup> [http://www.webmd.com/arthritis/tc/stages-of-lyme-disease-topic-overview] </sup> The late stage consists of the same symptoms but with increased intensity, where in some cases can lead to arthritis and deterioration of the nervous system <sup> [http://www.sciencedirect.com/science/article/pii/S1286457904000097] </sup>.
[[Image:skin rash lyme disease.jpg|thumb|150px|left|Figure 2. The skin rash characteristic to the early localized stage of Lyme disease. By James Gathany Content Providers(s): CDC/ James Gathany [Public domain], via Wikimedia Commons[https://upload.wikimedia.org/wikipedia/commons/0/01/Erythema_migrans_-_erythematous_rash_in_Lyme_disease_-_PHIL_9875.jpg]]]

===Host Immune System===

<br>Many of the symptoms of Lyme disease in humans are stemmed from the immunological [http://www.medicinenet.com/script/main/art.asp?articlekey=19510 inflammatory responses] of the bacteria in the affected areas <sup> [http://journals.cambridge.org/download.php?file=%2FERM%2FERM6_02%2FS1462399404007276a.pdf&code=0542aaff0efc740b1339879b90c07d0c] </sup>. When the body is attacked by foreign invaders, there are certain defenses that the body and its [http://en.wikipedia.org/wiki/Immune_system immune system] employs. A potential way <i> B. burgdorferi </i> is able to avoid detection and therefore attack by the human immune system is through [http://en.wikipedia.org/wiki/Molecular_mimicry mimicry]. It is possible that <i>B. burgdorferi </i> and self-proteins that are accepted by the body as its own, have been found to share similar [http://en.wikipedia.org/wiki/Epitope epitopes], which would aid the bacteria to be perceived as unthreatening <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC548028/pdf/0007-04.pdf] </sup>. As another player in the immune system, [http://en.wikipedia.org/wiki/Neutrophil_granulocyte neutrophils]  aid the human body in fighting infection. When <i> B. burgdorferi</i> colonizes inside the host’s body tissues, insufficient neutrophil activation and recruitment enhances the bacterium’s ability to survive in the host organism and surpass the immune system <sup> [http://www.jimmunol.org/content/178/8/5109] </sup>. The interactions between the host's immune system and <i> B. burgdorferi </i> are essential to the pathogenicity of the bacterium, seen in the research that shows host antibodies are able to kill <i> B. burgdorferi </i> in lab settings but not in vivo <sup> [http://www.sciencedirect.com/science/article/pii/S1286457904000097] </sup>.The host’s immune system and its responses to the bacteria determine the extent of the bacteria’s pathogenic potency. <i> B. burgdorferi</i>'s impact on various organisms such as mice, rabbits, hamsters, and monkeys have been widely studied. Different infectious consequences were seen in the different host organisms. Because of the varying laboratory results, Lyme disease is suggested to be more of a consequence of the host organism’s immunological responses to the bacteria rather than the bacteria’s strategy to be a pathogenic agent <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/] </sup>.<br>

==<b>Characteristics of <i> Borrelia burgdorferi </i></b>==

===Morphology=== 
[[Image:SpirochaeteSchemamobilityFL.jpg|thumb|256px|right|Figure 3. The morphology of spirochete bacteria and its internal flagella. By Lamiot (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons]]
<i> B. burgdorferi </i> are [http://en.wikipedia.org/wiki/Spirochaete spirochete bacteria], which are spirally shaped and have flagella that are enclosed between its inner and outer membranes (Figure 3). The flagella of <i> B. burgdorferi </i> are less subject to environmental factors because the flagella are protected by the double membrane structure.The bacterium’s flagella run lengthwise, rather than branch out into the environment like other bacteria, which allows for <i> B. burgdorferi </i> to better move through harder to maneuver conditions than other bacteria <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/] </sup>.

===Genome===

The genome of <i>B. burgdorferi </i>is comparably small to other free-living bacteria, similar to genome sizes of parasites and relies on the host for necessary metabolic machinery <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/] </sup>. The genome consists of a linear chromosome of 910, 725 base pairs and at least 17 linear and circular [http://en.wikipedia.org/wiki/Plasmid plasmids] <sup> [http://www.nature.com/nature/journal/v390/n6660/full/390580a0.html] </sup>. 
Because <i> B. burgdorferi </i> has a relatively small genome, the genes that are present are important for its success, where the genome has approximately 150 lipoprotein coding genes <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC517580/pdf/0733-04.pdf] </sup> and over 6% of its chromosomal genome is linked to its mobility <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/]</sup>.

==<b>Adaptive Gene Expression</b>==
===Physiological Conditions===
[[Image:journal.pone.0083276.g003 copy.png|thumb|500px|right| Figure 4. Induction of spirochete death by inducing RpoS expression. By Chen L., et al.  [Open Access], via PLOS One.[http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083276]]]

Surface proteins facilitate the interactions between the cell and its environment. <i> B. burgdorferi </i> is highly skilled in expressing certain surface proteins, altering the cell's interaction with its surroundings. In <i> B. burgdorferi </i>, two specific genes. the [http://en.wikipedia.org/wiki/RpoS rpoS] and [http://en.wikipedia.org/wiki/RpoN rpoN] genes, have been found to control signal cascades that regulate the assembly of various lipoproteins and surface proteins such as OspA and OspC, influencing communication with the environment and driving responses to changing conditions <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/] </sup>. By inducing RpoS expression, various intracellular pathways are prompted, resulting in rapid growth in cell numbers until mass cell death <sup> [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083276] </sup>. The OspA and OspC protein production pathway are important to the development of <i> B. burgdorferi </i> infections. OspA is a lipoprotein at the surface of the cell membrane and the expression of OspA decreases and OspC increases during the initial bacterial infection of the host by the tick <sup> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666356/pdf/nihms97697.pdf] </sup>. Higher levels of gene expression for the OspC protein are present in the nymphal stage of the tick life cycle than in the larvae and adult stages (Figure 5).  <sup> [http://www.sciencedirect.com/science/article/pii/S1286457901014356] </sup>. Ticks in the nymphal stage are the primary agents of infection, which suggests that OspC might have a role in the bacteria’s pathogeny. <i> B. burgdorferi</i>'s proficiency in gene expression allows for its proliferation despite changing environmental factors. 

[[Image: 1471-2180-12-44-2 copy.jpg|thumb|567px|left|Figure 5. A)PCR analysis of ospC transcription before and after tick transmission. B)PCR analysis of ospC transcription in the skin, heart, and bladder in mice at different number of days. By Ouyand et. al, BMC Microbiology 2012 12:44 do:10.1186/1471-2180-12-44. Open Access [http://www.biomedcentral.com/1471-2180/12/44]]]

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===Environmental Conditions===
<i> B. burgdorferi </i> has the ability to transform into [http://en.wikipedia.org/wiki/Microbial_cyst cysts] in vitro and in vivo, triggered by environmental stressors. [http://en.wikipedia.org/wiki/Oxidative_stress Oxidative stress] and extreme pH in terms of both acidity and alkalinity resulted in rapid transformations into cysts <sup> [http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0463.2004.apm1120110.x/epdf] </sup>. The conversion to the cystic form from the normal spirochete structure demonstrates the ability of <i> B. burgdorferi </i> to alter gene expression and adapt to changing environmental conditions, allowing for an increased chance to survive in adverse conditions.

==Further Reading==

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC517580/pdf/0733-04.pdf: <i> Borrelia burgdorferi</i> Changes Its Surface Antigenic Expression in Response to Host Immune Responses] Infection and Immunity

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC266316/pdf/jcm00075-0101.pdf: <i>Borrelia burgdorferi</i>, the Lyme Disease Agent] Journal of Clinical Microbiology, American Society for Microbiology

[http://en.wikipedia.org/wiki/Lyme_disease_controversy: Lyme disease controversy]

[http://jme.oxfordjournals.org/content/jmedent/41/2/226.full.pdf: Lyme Disease Spirochete, <i>Borrelia burgdorferi </i>, Endemic in Epicenter at Turkey Point, Ontario] Journal of Medical Entomolgy

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2870557/: The Lyme vaccine: a cautionary tale] Epidemiology and Infection

==References==

[http://www.niaid.nih.gov/topics/lymedisease/understanding/Pages/intro.aspx A History of Lyme Disease, Symptoms, Diagnosis, Treatment, and Prevention]. National Institute of Allergy and Infectious Diseases. (2012).

[http://www.biomedcentral.com/1471-2180/12/44 Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi] Ouyang, Z., Narasimhan, S., Neelakanta, G., Kumar, M., Utpal, P., Fikrig, E., Norgard, M.  BMC Microbiology. (2012). Volume 12.

[http://www.sciencedirect.com/science/article/pii/S1286457901014356 Analysis of Borrelia burdoferi gene expression during life cycle phases of the tick vector Ixodes scapularis]. Gilmore, R., Mbow, M., Stevenson, B.Microbes and Infection. (2001). Volume 3. p. 799-808.

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440571/ Biology of Infection with Borrelia burgdorferi]. Tilly, K., Rosa, P., Stewart, P. Infectious Disease Clinics of North America. (2008). Volume 22. p. 217-234.

[http://www.antimicrobe.org/new/b84.asp#t5 Borrelia burgdorferi (Lyme Disease)] Shapiro, E., Auwaerter, P. Infectious Diseases: Antimicrobial Agents. (2002).

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC548028/pdf/0007-04.pdf Evidence of <i> Borrelia </i> Autoimmunity-Induced Component of Lyme Carditis and Arthritis]. Raveche, E., Schutzer, S., Fernandes, H., Bateman, H., McCarthy, B., Nickell, S., Cunningham, M. Journal of Clinical Microbiology. (2005). 43(2) p. 850-856.

[http://www.nature.com/nature/journal/v390/n6660/full/390580a0.html Genomic sequence of a Lyme disease spirchoaete,<i> Borrelia burgdorferi </i>]. Fraser, C., et al. Nature. (1997). p. 580-586.

[http://www.jimmunol.org/content/178/8/5109 Increasing the Recruitment of Neutrophils to the Site of Infection Dramatically Attenuates <i> Borrelia burgdorferi </i> Infectivity].  Xu, Q., Seemanapalli, S., Reif. K., Brown, C., Liang, F. The Journal of Immunology. (2007). 178(8) p. 5109-5115.

[http://www.ncbi.nlm.nih.gov/pubmed/14961976 Induction of cystic forms by different stress conditions in <i> Borrelia burgdorferi </i>]. Murgia, R., Cinco, M. APMIS. (2004). 112(1): p.57-62.

[https://naturalmedicines.therapeuticresearch.com/databases/medical-conditions/l/lyme-disease.aspx  Lyme disease]. Natural Medicines. (2015).

[http://www.austincc.edu/microbio/2704x/bb.htm Lyme Disease]. Torrentera, L.

[http://lymepeople.com/lyme-disease-is-found-worldwide/ Lyme Disease is Found Worldwide]. (2014).

[http://journals.cambridge.org/download.php?file=%2FERM%2FERM6_02%2FS1462399404007276a.pdf&code=0542aaff0efc740b1339879b90c07d0c Lyme borreliosis (Lyme disease): molecular and cellular pathobiology and prospects for prevention, diagnosis and treatment]. Auwaerter, P., Aucott, J., Dumler, J. Expert Reviews in Molecular Medicine. (2004). 6(2).

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666356/pdf/nihms97697.pdf Outer membrane proteins of pathogenic spirochetes]. Cullen, P., Haake, D., Adler, B. FEMS Microbiology Review. (2004). 28(3): p. 291-218.

[http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/205_212.Rupprecht.00091.PDF The Pathogenesis of Lyme Neuroborreliosis: From Infection to Inflammation]. Rupprecht, T., Koedel, U., Fingerle, V., Pfister H. Molecular Medicine. (2008). 14(3-4) p. 205-212.

[http://www.webmd.com/arthritis/tc/stages-of-lyme-disease-topic-overview Stages of Lyme Disease]. WedMD Medical Reference. (2012).

[http://www.sciencedirect.com/science/article/pii/S1286457904000097 Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease].  Embers, M., Ramamoorthy, R., Philipp, M.Microbes and Infection. (2004). Volume 6. p. 312-318.



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Edited by Jenny Han, a student of [http://www.jsd.claremont.edu/faculty/profile.asp?FacultyID=274 Suzanne Kern] in BIOL168L (Microbiology) in [http://www.jsd.claremont.edu/ The Keck Science Department of the Claremont Colleges] Spring 2015.

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