Borrelia burgdorferi

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Borrelia burgdorferi
Scientific classification
Kingdom: Bacteria
Phylum: Spirochaetes
Class: Spirochaetes
Order: Spirochaetales
Genus: Borrelia
Species: B. burgdorferi
Binomial name
Borrelia burgdorferi

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Lyme disease.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2] Template:Seealso Template:Seealso (a newly discovered Borrelia species that has been associated with Lyme disease)

Overview

Borrelia burgdorferi is species of bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease. It is a zoonotic, vector-borne disease transmitted by ticks and is named after the researcher Willy Burgdorfer who first isolated the bacterium in 1982. B. burgdorferi is one of the few pathogenic bacteria that can survive without iron, having replaced all of its iron-sulphur cluster enzymes with enzymes that use manganese, thus avoiding the problem many pathogenic bacteria face in acquiring iron. B. burgdorferi infections have been linked to non-Hodgkin lymphomas.[1]

Organism

Borrelia burgdorferi the causative agent of Lyme disease (borreliosis). Magnified 400 times.
  • Borrelia are microaerophillic and slow-growing—the primary reason for the long delays when diagnosing Lyme disease—and have been found to have greater strain diversity than previously estimated.[2] The strains differ in clinical symptoms and/or presentation as well as geographic distribution.[3]
  • Except for Borrelia recurrentis (which causes louse-borne relapsing fever and is transmitted by the human body louse), all known species are believed to be transmitted by ticks.[4]
  • A second, a new organism has been reported for causing Lyme disease.
  • Borrelia mayonii causes similar symptoms to Borrelia burgdorferi. However unlike B. burgdorferi, B. mayonii may induce a quick onset of nausea and vomiting.
  • The rash associated with this new organism is also different from the conventional, bulls-eye rash.
  • The rash associated with B. mayonii has been reported as a diffuse rash, covering the entire body in "red spots." [5]

Structure and growth

B. burgdorferi is a highly specialized, motile, two-membrane, spiral-shaped spirochete ranging from about 9 to 32 micrometers in length. It is often described as gram-negative and has an outer membrane with lipopolysaccharide (LPS), though it stains only weakly in the Gram stain. B. burgdorferi is a microaerophilic organism, requiring little oxygen to survive. It lives primarily as an extracellular pathogen, although it can also hide intracellularly (see Mechanisms of persistence section).

Like other spirochetes such as T. pallidum (the agent of syphilis), B. burgdorferi has an axial filament composed of flagella which run lengthways between its cell wall and outer membrane. This structure allows the spirochete to move efficiently in corkscrew fashion through viscous media, such as connective tissue. As a result, B. burgdorferi can disseminate throughout the body within days to weeks of infection, penetrating deeply into tissue where the immune system and antibiotics may not be able to eradicate the infection.

B. burgdorferi is very slow growing, with a doubling time of 12-18 hours[6] (in contrast to pathogens such as Streptococcus and Staphylococcus, which have a doubling time of 20-30 minutes). Since most antibiotics kill bacteria only when they are dividing, this longer doubling time necessitates the use of relatively longer treatment courses for Lyme disease. Antibiotics are most effective during the growth phase, which for B. burgdorferi occurs in four-week cycles.

Outer surface proteins

The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) that have been characterized (OspA through OspF). They are presumed to play a role in virulence.

OspA and OspB are by far the most abundant outer surface proteins.

The OspA and OspB genes encode the major outer membrane proteins of the B burgdorferi. The two Osp proteins show a high degree of sequence similarity, indicating a recent evolutionary event. Molecular analysis and sequence comparison of OspA and OspB with other proteins has revealed similarity to the signal peptides of prokaryotic lipoproteins.[7]Virtually all spirochetes in the midgut of an unfed nymph tick express OspA.

OspC is an antigen-detection of its presence by the host organism and can stimulate an immune response. While each individual bacterial cell contains just one copy of the gene encoding OspC, populations of B. burgdorferi have shown high levels of variation among individuals in the gene sequence for OspC.[8] OspC is likely to play a role in transmission from vector to host, since it has been observed that the protein is only expressed in the presence of mammalian blood or tissue.[9]

The functions of OspD are unknown.

OspE and OspF are structurally arranged in tandem as one transcriptional unit under the control of a common promoter.[10]

In transmission to the mammaliam host, when the nymphal tick begins to feed, and the spirochetes in the midgut begin to multiply rapidly, most spirochetes cease expressing OspA on their surface. Simultaneous with the disappearance of OspA, the spirochete population in the midgut begins to express a OspC. Upregulation of OspC begins during the first day of feeding and peaks 48 hours after attachment.[11]

Differentiating B. burgdorferi from B. mayonii

The following table demonstrates key clinical and epidemiological features that distinguish B. burgdorferi from B. mayonii:[12]

B. burgdorferi B. mayonii
Transmission Tick bite Tick bite
Distribution in the USA Northeast, Mid-Atlantic, and Midwest regions Midwest region
Bacteria Concentration in Blood (Spirochetemia) Lower Higher
Early Symptoms Fever, headache, rash, neck pain Fever, headache, rash, neck pain
Late Symptoms Arthritis Arthritis
Nausea / Vomiting? No Yes
Rash Characteristics Bull's-eye target lesion Diffuse rash
Diagnosis Serology or PCR Serology or PCR
Treatment Doxycycline Doxycycline

Adapted from Pritt BS et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infectious Diseases. DOI: http://dx.doi.org/10.1016/S1473-3099(15)00464-8[12] | Centers for Disease Control and Prevention (CDC). New Lyme-disease-causing bacteria species discovered. URL: http://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html. Retrieved February 9th 2016.[13]

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References

  1. Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R (2006). "Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives". Clinical lymphoma & myeloma. 6 (4): 289–300. PMID 16507206.
  2. Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, Barbour AG (2004). "Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe" (PDF). Microbiology. 150 (Pt 6): 1741–55. PMID 15184561.
  3. Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. ISBN 0-8385-8529-9.
  4. Felsenfeld O (1971). Borrelia: Strains, Vectors, Human and Animal Borreliosis. St. Louis: Warren H. Green, Inc.
  5. CBS News Lyme Disease. http://www.cbsnews.com/news/lyme-disease-just-got-nastier/ Accessed February 9, 2016.
  6. Kelly, R. T. (1984). Genus IV. Borrelia Swellengrebel 1907, 582AL. In Bergey's Manual of Systematic Bacteriology, vol. 1, pp. 57–62. Edited by N. R. Krieg & J. G. Holt. Baltimore: Williams & Wilkins.
  7. Bergstrom S. , Bundoc V.G. , Barbour A.G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol. Microbiol. 3 479-486 1989
  8. Girschick, J. and Singh, S.E. Molecular survival strategies of the lyme disease spirochete Borrelia burgdorferi. Sep, 2004. The Lancet Infectious Diseases: Volume 4, Issue 9, September 2004, Pages 575-583.
  9. Fikrig, E. and Pal, U. Adaptation of Borrelia burgdorferi in the vector and vertebrate host. Microbes and Infection Volume 5, Issue 7, June 2003, Pages 659-666. PMID 12787742
  10. Lam TT, Nguyen TP, Montgomery RR, Kantor FS, Fikrig E, Flavell RA. Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun. 1994 Jan;62(1):290-8.
  11. Schwan TG, Piesman J. Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J Clin Microbiol 2000;38:382-8.
  12. 12.0 12.1 Pritt, BS; Mead, PS (Feb 5 2016). "Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study" (PDF). Lancet Infectious Diseases. doi:http://dx.doi.org/10.1016/S1473-3099(15)00464-8 Check |doi= value (help). Retrieved 9 February 2016. Check date values in: |date= (help)
  13. New Lyme-disease-causing bacteria species discovered - Centers for Disease Control and Prevention (CDC) http://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html Accessed on Feb 9 2016
  14. 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 14.13 14.14 14.15 14.16 14.17 14.18 14.19 14.20 14.21 14.22 14.23 14.24 14.25 14.26 14.27 14.28 14.29 14.30 14.31 14.32 14.33 14.34 14.35 14.36 14.37 14.38 14.39 14.40 14.41 14.42 14.43 "Public Health Image Library (PHIL)".

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