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Lyme disease microbiology



  Lyme disease, or borreliosis, is caused by Gram negative spirochetal bacteria from the genus Borrelia, which has at least 37 known species, 12 of which are Lyme related, and an unknown number of genomic strains. Borrelia species known to cause Lyme disease are collectively known as Borrelia burgdorferi sensu lato.

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.[1] The strains differ in clinical symptoms and/or presentation as well as geographic distribution.[2]

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.[3]

Contents

Species and strains

Until recently it was thought that only three genospecies caused Lyme disease (borreliosis): B. burgdorferi sensu stricto ( the predominant species in North America, but also present in Europe); B. afzelii; and B. garinii (both predominant in Eurasia). The complete genomes of B. burgdorferi sensu stricto strain B31, B. afzelii strain PKo and B. garinii strain PBi are known. B. burgdorferi strain B31 was derived by limited dilutional cloning from the original Lyme-disease tick isolate derived by Alan Barbour. There are over 300 species or strains of Borrelia worldwide with approximately 100 in the U.S., and it is unknown how many cause Lyme-like sickness, but many of them may do so.

At present, diagnostic tests are based only on B. burgdorferi sensu stricto (the only species used in the U.S.), B. afzelii, and B. garinii.

Emerging genospecies

  • B. valaisiana was identified as a genomic species from Strain VS116, and named B. valaisiana in 1997.[4] It was later detected by polymerase chain reaction (PCR) in human cerebral spinal fluid (CSF) in Greece.[5] B. valaisiana has been isolated throughout Europe, as well east Asia.[6]

Newly discovered genospecies have also been found to cause disease in humans:

  • B. lusitaniae [7] in Europe (especially Portugal), North Africa and Asia.
  • B. bissettii [8][9] in the U.S. and Europe.

Additional B. burgdorferi sensu lato genospecies suspected of causing illness, but not confirmed by culture, include B. japonica, B. tanukii and B. turdae (Japan); B. sinica (China); and B. andersonii (U.S.). Some of these species are carried by ticks not currently recognized as carriers of Lyme disease.

The B. miyamotoi spirochete, related to the relapsing fever group of spirochetes, is also suspected of causing illness in Japan. Spirochetes similar to B. miyamotoi have recently been found in both I. ricinus ticks in Sweden and I. scapularis ticks in the U.S.[12][13]

B. lonestari

Apart from this group of closely related genospecies, additional Borrelia species of interest include B. lonestari, a spirochete recently detected in the Amblyomma americanum tick (Lone Star tick) in the U.S.[14] B. lonestari is suspected of causing STARI (Southern Tick-Associated Rash Illness), also known as Masters disease in honor of its discoverer Ed Masters. The illness follows a Lone Star tick bite and clinically resembles Lyme disease, but sufferers usually test negative for Lyme.[15]There is currently no diagnostic test available for STARI/Masters, and no official treatment protocol, though antibiotics are generally prescribed.

Epidemiology

The number of reported cases of the Lyme disease (borreliosis) have been increasing, as are endemic regions in North America. Of cases reported to the United States Centers for Disease Control and Prevention (CDC), the rate of Lyme disease infection is 7.9 cases for every 100,000 persons. In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.[16] Although Lyme disease has now been reported in 49 of 50 states in the U.S, about 99% of all reported cases are confined to just five geographic areas (New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central).[17]

In Europe, cases of B. burgdorferi sensu lato infected ticks are found predominantly in Norway, Netherlands, Germany, France, Italy, Slovenia, and Poland, but have been isolated in almost every country on the continent. Lyme disease statistics for Europe can be found at Eurosurveillance website.

Borrelia burgdorferi sensu lato infested ticks are being found more frequently in Japan, as well as in Northwest China and far eastern Russia.[18][19] Borrelia has been isolated in Mongolia as well.[20]

In South America, tick-borne disease recognition and occurrence is rising. Ticks carrying Borrelia burgdorferi sensu lato, as well as canine and human tick-borne disease, have been reported widely in Brazil, but the subspecies of Borrelia has not yet been defined.[21] The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo.[22] Borrelia burgdorferi sensu stricto antigens in patients have been identified in Colombia and in Bolivia.

In Northern Africa, Borrelia burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.[23][24][25]

In Western Africa and Sub-Saharan Africa, tick-borne relapsing fever has been recognized for over a century, first isolated by the British physicians Joseph Dutton and John Todd in 1905. Borrelia in the manifestation of Lyme disease in this region is presently unknown but evidence indicates that the disease may occur in humans in sub-Saharan Africa. The abundance of hosts and tick vectors would favor the establishment of the infection in Africa.[26] In East Africa two cases of Lyme disease have been reported in Kenya.[27]

In Australia there is no definitive evidence for the existence of B. burgdorferi or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease.[28] Cases of neuroborreliois have been documented in Australia but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.

To date, data show that Northern hemisphere temperate regions are most endemic for Lyme disease.[29][30]

Life cycle

Further information: Tick#Life cycle

The life-cycle of B. burgdorferi is complex, requiring ticks, rodents, and deer at various points. Mice are the primary reservoir for the bacteria; Ixodes ticks then transmit the B. burgdorferi infection to deer.

Hard ticks have a variety of life histories with respect to optimizing their chance of contact with an appropriate host to ensure survival. The life stages of soft ticks are not readily distinguishable. The first life stage to come out of the egg, a six legged larva, takes a blood meal from a host, and molts to the first nymphal stage. Unlike hard ticks, many soft ticks go through multiple nymphal stages, gradually increasing in size until the final molt to the adult stage.

The life cycle of the deer tick comprises three growth stages: the larva, nymph and adult.

The life-cycle concept encompassing reservoirs and infections in multiple hosts has recently been expanded to encompass forms of the spirochete which differ from the motile corkscrew form, and these include cystic forms spheroplast-like, straighted non-coiled bacillary forms which are immotile due to flagellin mutations and granular forms coccoid in profile. The model of Plasmodium species Malaria with multiple parasitic profiles demonstrable in various host insects and mammals is a hypothesized model for a similarly complex proposed Borrelia spirochete life cycle.[31][32]

Whereas B. burgdorferi is most associated with deer tick and the white footed mouse,[33] B. afzelii is most frequently detected in rodent-feeding vector ticks, B.garinii and B. valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for Borrelia burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative immune complement pathway of various host species may determine its reservoir host association.

Genomic characteristics

The genome of B. burgdorferi (B31 strain) was the third microbial genome ever to be sequenced, following the sequencing of both H.influenzae and M.genitalium in 1995, and contains 910,725 base pairs and 853 genes.[34] One of the most striking features of B. burgdorferi as compared with other eubacteria is its unusual genome, which is far more complex than that of its spirochetal cousin Treponema pallidum, the agent of syphilis.[35] The genome of B. burgdorferi includes a linear chromosome approximately one megabase in size, with 21 plasmids (12 linear and 9 circular) - by far the largest number of plasmids found in any known bacterium.[36] Genetic exchange, including plasmid transfers, contributes to the pathogenicity of the organism.[37] Long-term culture of B. burgdorferi results in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in virulence.

Chemical analysis of the external membrane of B. burgdorferi revealed the presence of 46% proteins, 51% lipids and 3% carbohydrates.[38]

Structure and growth

B. burgdorferi is a highly specialized, motile, two-membrane, flat-waved spirochete ranging from about 9 to 32 micrometers in length.[39] It is often described as gram-negative, though it stains weakly in the Gram stain. The bacterial membranes in at least the B31, NL303 and N40 strains of B. burgdorferi do not contain lipopolysaccharide which is extremely atypical for gram-negative bacteria; instead, the membranes contain glycolipids.[40] However, the membranes in the B31 strain have been found to contain a lipopolysaccharide-like component.[41] B. burgdorferi is a microaerophilic organism, requiring little oxygen to survive. Unlike most bacteria, B. burgdorferi does not utilize iron, hence avoiding the difficulty of acquiring iron during infection.[42] 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[43] (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.[citation needed]

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). The Osp proteins are lipoproteins anchored by N-terminally attached fatty acid molecules to the membrane.[44] They are presumed to play a role in virulence, transmission, or survival in the tick.

OspA, OspB, and OspD are expressed by B. burgdorferi residing in the gut of unfed ticks, suggesting that they promote the persistence of the spirochete in ticks between blood meals.[45][46]

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 duplication event.[47] Virtually all spirochetes in the midgut of an unfed nymph tick express OspA. OspA promotes the attachment of B. burgdorferi to the tick protein TROSPA, present on tick gut epithelial cells.[48] OspB also has an essential role in the adherence of B. burgdorferi to the tick gut.[49] Although OspD has been shown to bind to tick gut extracts in vitro as well as OspA and OspB, it is not essential for the attachment and colonization of the tick gut, and it is not required for human infections.[46]

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.[50] 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.[51]

OspE and OspF were initially identified in B. burgdorferi strain N40.[52] The ospE and ospF genes are structurally arranged in tandem as one transcriptional unit under the control of a common promoter.[52] It is now known that individual strains of B. burgdorferi carry multiple related copies of the ospEF locus, which are now collectively referred to as erp (OspE/F-like related protein). In B. burgdoreri strains B31 and 297, most of the erp loci occupy the same position on the multiple copies of the cp32 plasmid present in these strains.[53] Each erp locus consists of one or two erp genes. When two genes are present, they are transcribed as one operon, although in some cases, an internal promoter in the first gene may also transcribe the second gene.[54] The presence of multiple Erp proteins was proposed to be important in allowing B. burgdorferi to evade killing by the alternative complement pathway of a broad range of potential animal hosts, as individual Erp proteins exhibited different binding patterns to the complement regulator factor H from different animals.[55] However, it was recently demonstrated that the presence of factor H is not necessary to enable B. burgdorferi to infect mice, suggesting that the Erp proteins have an additional function[56]

In transmission to the mammalian 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.[57]

Mechanisms of persistence

While B. burgdorferi is susceptible to a number of antibiotics in vitro, there are contradictory reports as to the efficacy of antibiotics in vivo. B. burgdorferi may persist in humans and animals for months or years despite a robust immune response and standard antibiotic treatment, particularly when treatment is delayed and dissemination widespread. Numerous studies have demonstrated persistence of infection despite antibiotic therapy.[58][59][60]

Various survival strategies of B. burgdorferi have been posited to explain this phenomenon,[61] including the following:

  • Intracellular invasion.

B. burgdorferi has been shown to invade a variety of cells, including endothelium,[64] fibroblasts,[65] lymphocytes,[66] macrophages,[67] keratinocytes,[68] synovium,[69][70] and most recently neuronal and glial cells. [71] By 'hiding' inside these cells, B. burgdorferi is able to evade the immune system and is protected to varying degrees against antibiotics,[72][73] allowing the infection to persist in a chronic state.

  • Altered morphological forms, i.e. spheroplasts (cysts, granules).

The existence of B. burgdorferi spheroplasts, which lack a cell wall, has been documented in vitro,[74][75][76][77] in vivo,[70][75][78] and in an ex vivo model.[79] The fact that energy is required for the spiral bacterium to convert to the cystic form[74] suggests that these altered forms have a survival function, and are not merely end stage degeneration products. The spheroplasts are indeed virulent and infectious, able to survive under adverse environmental conditions, and have been shown to revert back to the spiral form in vitro, once conditions are more favorable.[80][81]

A number of other factors make B. burgdorferi spheroplasts a key factor in the relapsing, chronic nature of Lyme disease. Compared to the spiral form, spheroplasts have dramatically reduced surface area for immune surveillance. They also express different surface proteins — another reason for seronegative disease (i.e. false-negative antibody tests), as current tests only look for antibodies to surface proteins of the spiral form. In addition, B. burgdorferi spheroplasts are generally not susceptible to the antibiotics traditionally used for Lyme disease. They have instead shown sensitivity in vitro to antiparasitic drugs such as metronidazole,[82] tinidazole,[83] and hydroxychloroquine [84] to which the spiral form of B. burgdorferi is not sensitive.

Like the Borrelia that cause relapsing fever, B. burgdorferi has the ability to vary its surface proteins in response to immune attack.[61][85] This ability is related to the genomic complexity of B. burgdorferi, and is another way B. burgdorferi evades the immune system to establish a chronic infection.[86]

Complement inhibition, induction of anti-inflammatory cytokines such as IL-10, and the formation of immune complexes have all been documented in B. burgdorferi infection.[61] Furthermore, the existence of immune complexes provides another explanation for seronegative disease (i.e. false-negative antibody tests of blood and cerebrospinal fluid), as studies have shown that substantial numbers of seronegative Lyme patients have antibodies bound up in these complexes.[87]

Advancing immunology research

Further information: Lyme Disease#Advancing Immunology Research

The role of T cells in Borrelia was first made in 1984,[88] the role of cellular immunity in active Lyme disease was made in 1986,[89] and long term persistence of T cell lymphocyte responses to B. burgdorferi as an "immunological scar syndrome" was hypothesized in 1990.[90] The role Th1 and interferon-gamma (INF-gamma) in Borrelia was first described in 1995.[91] The cytokine pattern of Lyme disease, and the role of Th1 with down regulation of interleukin-10 (IL-10) was first proposed in 1997.[92]

Recent studies in both acute and antibiotic refractory, or chronic, Lyme disease have shown a distinct pro-inflammatory immune process. This pro-inflammatory process is a cell-mediated immunity and results in Th1 upregulation. These studies have shown a significant decrease in cytokine output of (IL-10), an upregulation of Interleukin-6 (IL-6) and Interleukin-12 (Il-12) and Interferon-gamma (IFN-gamma) and disregulation in TNF-alpha predominantly.

New research has also found that chronic Lyme patients have higher amounts of Borrelia-specific forkhead box P3 (FoxP3) than healthy controls, indicating that regulatory T cells might also play a role, by immunosuppression, in the development of chronic Lyme disease. FoxP3 are a specific marker of regulatory T cells.[93] The signaling pathway P38 mitogen-activated protein kinases (p38 MAP kinase) has also been identified as promoting expression of proinflammatory cytokines from borrelia.[94][95]

The culmination of these new and ongoing immunological studies suggest this cell-mediated immune disruption in the Lyme patient amplifies the inflammatory process, often rendering it chronic and self-perpetuating, regardless of whether the Borrelia bacterium is still present in the host, or in the absence of the inciting pathogen in an autoimmune pattern.[96]

References

  1. ^ Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, and 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.
  2. ^ Ryan KJ and Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9. 
  3. ^ Felsenfeld O (1971). Borrelia: Strains, Vectors, Human and Animal Borreliosis. St. Louis: Warren H. Green, Inc. 
  4. ^ Wang G, van Dam AP, Le Fleche A, et al (1997). "Genetic and phenotypic analysis of Borrelia valaisiana sp. nov. (Borrelia genomic groups VS116 and M19)". Int. J. Syst. Bacteriol. 47 (4): 926-932. PMID 9336888.
  5. ^ Diza E, Papa A, Vezyri E, Tsounis S, Milonas I, and Antoniadis A (2004). "Borrelia valaisiana in cerebrospinal fluid". Emerging Infect. Dis. 10 (9): 1692-1693. PMID 15503409.
  6. ^ Masuzawa T (2004). "Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia". Jpn. J. Infect. Dis. 57 (6): 229-235. PMID 15623946.
  7. ^ Collares-Pereira M, Couceiro S, Franca I, Kurtenbach K, Schafer SM, Vitorino L, Goncalves L, Baptista S, Vieira ML, and Cunha C (2004). "First isolation of Borrelia lusitaniae from a human patient" (PDF). J Clin Microbiol 42 (3): 1316-1318. PMID 15004107.
  8. ^ Postic D, Ras NM, Lane RS, Hendson M, and Baranton G (1998). "Expanded diversity among Californian Borrelia isolates and description of Borrelia bissettii sp. nov. (formerly Borrelia group DN127)" (PDF). J Clin Microbiol 36 (12): 3497-3504. PMID 9817861.
  9. ^ Maraspin V, Cimperman J, Lotric-Furlan S, Ruzic-Sabljic E, Jurca T, Picken RN, Strle F (2002). "Solitary borrelial lymphocytoma in adult patients". Wien Klin Wochenschr 114 (13-14): 515-523. PMID 12422593.
  10. ^ Richter D, Postic D, Sertour N, Livey I, Matuschka FR, and Baranton G (2006). "Delineation of Borrelia burgdorferi sensu lato species by multilocus sequence analysis and confirmation of the delineation of Borrelia spielmanii sp. nov". Int J Syst Evol Microbiol 56 (Pt 4): 873-881. PMID 16585709.
  11. ^ Foldvari G, Farkas R, and Lakos A (2005). "Borrelia spielmanii erythema migrans, Hungary". Emerg Infect Dis 11 (11): 1794-1795. PMID 16422006.
  12. ^ Scoles GA, Papero M, Beati L, and Fish D (2001). "A relapsing fever group spirochete transmitted by Ixodes scapularis ticks". Vector Borne Zoonotic Dis 1 (1): 21-34. PMID 12653133.
  13. ^ Bunikis J, Tsao J, Garpmo U, Berglund J, Fish D, and Barbour AG (2004). "Typing of Borrelia relapsing fever group strains". Emerg Infect Dis 10 (9): 1661-1664. PMID 15498172.
  14. ^ Varela AS, Luttrell MP, Howerth EW, Moore VA, Davidson WR, Stallknecht DE, and Little SE (2004). "First culture isolation of Borrelia lonestari, putative agent of southern tick-associated rash illness" (PDF). J Clin Microbiol 42 (3): 1163-1169. PMID 15004069.
  15. ^ Masters E, Granter S, Duray P, and Cordes P (1998). "Physician-diagnosed erythema migrans and erythema migrans-like rashes following Lone Star tick bites". Arch Dermatol 134 (8): 955-960. PMID 9722725.
  16. ^ DVBID: Disease Upward Climb - CDC Lyme Disease (2006-10-02). Retrieved on 2007-08-23.
  17. ^ Lyme Disease Statistics. Centers for Disease Control and Prevention (CDC) (2007-04-02). Retrieved on 2007-08-23.
  18. ^ Li M, Masuzawa T, Takada N, Ishiguro F, Fujita H, Iwaki A, Wang H, Wang J, Kawabata M, and Yanagihara Y (Jul 1998). "Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan". Appl Environ Microbiol 64 (7): 2705-2709.
  19. ^ Masuzawa T (Dec 2004). "Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia"". Jpn J Infect Dis. 57 (6): 229-235.
  20. ^ Walder G, Lkhamsuren E, Shagdar A, Bataa J, Batmunkh T, Orth D, Heinz FX, Danichova GA, Khasnatinov MA, Wurzner R, and Dierich MP (May 2006). "Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia". Int J Med Microbiol. 296 Suppl (40): 69-75.
  21. ^ Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi ML, and Yoshinari NH (Apr 2007). "Description of Lyme disease-like syndrome in Brazil: is it a new tick-borne disease or Lyme disease variation?". Braz J Med Biol Res. 40 (4): 443-456.
  22. ^ Yoshinari NH, Oyafuso LK, Monteiro FG, de Barros PJ, da Cruz FC, Ferreira LG, Bonasser F, Baggio D, and Cossermelli W (Jul-Aug 1993). "Lyme disease. Report of a case observed in Brazil". Rev Hosp Clin Fac Med Sao Paulo 48 (4): 170-174.
  23. ^ Bouattour A, Ghorbel A, Chabchoub A, Postic D (2004). "Lyme borreliosis situation in North Africa". Arch Inst Pasteur Tunis. 81 (1-4): 13-20.
  24. ^ Dsouli N, Younsi-Kabachii H, Postic D, Nouira S, Gern L, and Bouattour A (Jul 2006). "Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia burgdorferi sensu lato (Spirochaetaceae) in Tunisia". J Med Entomol. 43 (4): 737-742.
  25. ^ Helmy N (Aug 2000). "Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with Borrelia spirochetes in Egypt". J Egypt Soc Parasitol 30: 607-619.
  26. ^ Fivaz BH, Petney TN (Sep 1989). "Lyme disease — a new disease in southern Africa?". J S Afr Vet Assoc. 60 (3): 155-158.
  27. ^ Jowi JO and Gathua SN (May 2005). "Lyme disease: report of two cases". East Afr Med J. 82 (5): 267-269. PMID 16119758.
  28. ^ Piesman J, Stone BF (Feb 1991). "Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochete Borrelia burgdorferi". Int J Parasitol. 21 (1): 109-111. PMID 2040556.
  29. ^ Grubhoffer L, Golovchenko M, Vancova M, Zacharovova-Slavickova K, Rudenko N, Oliver JH Jr. (Nov 2005). "Lyme borreliosis: insights into tick-/host-borrelia relations". Folia Parasitol (Praha) 52 (4 (Review)): 279-294. PMID 16405291.
  30. ^ Higgins R (Aug 2004). "Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague". Rev Sci Tech. 23 (2): 569-581. PMID 15702720.
  31. ^ Macdonald AB (2006). "A life cycle for Borrelia spirochetes?". Med Hypotheses 67 (4): 810-818. PMID 16716532.
  32. ^ Lymeinfo.net — LDAdverseConditions (2006).
  33. ^ Wallis RC, Brown SE, Kloter KO, and Main AJ Jr. (Oct 1978). "Erythema chronicum migrans and Lyme arthritis: field study of ticks". Am J Epidemiol. 108 (4): 322-327. PMID 727201.
  34. ^ Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, van Vugt R, Palmer N, Adams MD, Gocayne J, Weidman J, Utterback T, Watthey L, McDonald L, Artiach P, Bowman C, Garland S, Fuji C, Cotton MD, Horst K, Roberts K, Hatch B, Smith HO, and Venter JC (1997). "Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi". Nature 190 (6660): 580-586. Retrieved on 2007-10-26.
  35. ^ Porcella SF and Schwan TG (2001). "Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms". J Clin Invest 107 (6): 651-6. PMID 11254661.
  36. ^ Casjens S, Palmer N, van Vugt R, Huang WM, Stevenson B, Rosa P, Lathigra R, Sutton G, Peterson J, Dodson RJ, Haft D, Hickey E, Gwinn M, White O, and Fraser CM (2000). "A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi". Mol Microbiol 35 (3): 490-516. PMID 10672174.
  37. ^ Qiu WG, Schutzer SE, Bruno JF, Attie O, Xu Y, Dunn JJ, Fraser CM, Casjens SR, and Luft BJ (2004). "Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing" (PDF). Proc Natl Acad Sci U S A 101 (39): 14150-5. PMID 15375210.
  38. ^ Schwarzová K (Jun 1993). "Lyme borreliosis: review of present knowledge". Cesk Epidemiol Mikrobiol Imunol. 42 (2): 87-92.
  39. ^ Goldstein SF, Charon NW, and Kreiling JA (1994). "Borrelia burgdorferi swims with a planar waveform similar to that of eukaryotic flagella". Proc. Natl. Acad. Sci. U.S.A. 91 (8): 3433–3437. PMID 8159765.
  40. ^ Ben-Menachem G, Kubler-Kielb J, Coxon B, Yergey A, and Schneerson R (2003). "A newly discovered cholesteryl galactoside from Borrelia burgdorferi". Proc. Natl. Acad. Sci. U.S.A. 100 (13): 7913–7918. doi:10.1073/pnas.1232451100. PMID 12799465.
  41. ^ Schwarzová K and Čižnár I (2004). "Immunochemical analysis of lipopolysaccharide-like component extracted from Borrelia burgdorferi sensu lato". Folia Microbiol. 49 (5): 625-629. Retrieved on 2007-10-26.
  42. ^ Posey JE and Gherardini FC (2000). "Lack of a role for iron in the Lyme disease pathogen". Science 288 (5471): 1651–3. PMID 10834845.
  43. ^ Kelly, RT (1984). in Krieg NR and Holt JG: Genus IV. Borrelia Swellengrebel 1907, 582AL. Williams & Wilkins: Baltimore, 57–62. 
  44. ^ Haake DA (2000). "Spirochaetal lipoproteins and pathogenesis". Microbiology (Reading, Engl.) 146 (Pt 7): 1491–1504. PMID 10878114.
  45. ^ Schwan TG, Piesman J, Golde WT, Dolan MC, and Rosa PA (1995). "Induction of an outer surface protein on Borrelia burgdorferi during tick feeding". Proc. Natl. Acad. Sci. U.S.A. 92 (7): 2909–2913. PMID 7708747.
  46. ^ a b Li X, Neelakanta G, Liu X, Beck DS, Kantor FS, Fish D, Anderson JF, and Fikrig E (2007). "Role of outer surface protein D in the Borrelia burgdorferi life cycle". Infect. Immun. 75 (9): 4237–4244. doi:10.1128/IAI.00632-07. PMID 17620358.
  47. ^ Bergström S, Bundoc VG, and Barbour AG (1989). "Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi". Mol. Microbiol. 3 (4): 479–486. PMID 2761388.
  48. ^ Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, Desilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, and Fikrig E (2004). "TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi". Cell 119 (4): 457–468. doi:10.1016/j.cell.2004.10.027. PMID 15537536.
  49. ^ Neelakanta G, Li X, Pal U, Liu X, Beck DS, DePonte K, Fish D, Kantor FS, and Fikrig E (2007). "Outer surface protein B is critical for Borrelia burgdorferi adherence and survival within Ixodes ticks". PLoS Pathog. 3 (3): e33. doi:10.1371/journal.ppat.0030033. PMID 17352535.
  50. ^ Girschick, J and Singh, SE (Sep 2004). "Molecular survival strategies of the lyme disease spirochete Borrelia burgdorferi". The Lancet Infectious Diseases 4 (9): 575-583.
  51. ^ Fikrig, E. and Pal, U (Jun 2003). "Adaptation of Borrelia burgdorferi in the vector and vertebrate host". Microbes and Infection 5 (7): 659-666. PMID 12787742.
  52. ^ a b Lam TT, Nguyen TP, Montgomery RR, Kantor FS, Fikrig E, and Flavell RA (1994). "Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease". Infect. Immun. 62 (1): 290–298. PMID 8262642.
  53. ^ Stevenson B, Zückert WR, and Akins DR (2000). "Repetition, conservation, and variation: the multiple cp32 plasmids of Borrelia species". J. Mol. Microbiol. Biotechnol. 2 (4): 411–422. PMID 11075913.
  54. ^ Stevenson B, Bono JL, Schwan TG, and Rosa P (1998). "Borrelia burgdorferi Erp proteins are immunogenic in mammals infected by tick bite, and their synthesis is inducible in cultured bacteria". Infect. Immun. 66 (6): 2648–2654. PMID 9596729.
  55. ^ Stevenson B, El-Hage N, Hines MA, Miller JC, and Babb K (2002). "Differential binding of host complement inhibitor factor H by Borrelia burgdorferi Erp surface proteins: a possible mechanism underlying the expansive host range of Lyme disease spirochetes". Infect. Immun. 70 (2): 491–497. PMID 11796574.
  56. ^ Woodman ME, Cooley AE, Miller JC, Lazarus JJ, Tucker K, Bykowski T, Botto M, Hellwage J, Wooten RM, and Stevenson B (2007). "Borrelia burgdorferi binding of host complement regulator factor H is not required for efficient mammalian infection". Infect. Immun. 75 (6): 3131–3139. doi:10.1128/IAI.01923-06. PMID 17420242.
  57. ^ Schwan TG and Piesman J (2000). "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 38: 382-388.
  58. ^ Bayer ME and Zhang L, Bayer MH (1996). "Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases". Infection 24 (5): 347-353. PMID 8923044.
  59. ^ Preac-Mursic V, Weber K, Pfister HW, et al (1989). "Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis". Infection 17 (6): 355-359. PMID 2613324.
  60. ^ Oksi J, Marjamaki M, Nikoskelainen J, and Viljanen MK (1999). "Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis". Ann Med 31 (3): 225-232. PMID 10442678.
  61. ^ a b c Embers ME, Ramamoorthy R, and Philipp MT (2004). "Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease". Microbes Infect 6 (3): 312-318. PMID 15065567.
  62. ^ Miklossy J, Khalili K, Gern L, et al (2004). "Borrelia burgdorferi persists in the brain in chronic Lyme neuroborreliosis and may be associated with Alzheimer disease". J Alzheimers Dis 6 (6): 639-649; discussion 673-681. PMID 15665404.
  63. ^ Grab DJ, Perides G, Dumler JS, Kim KJ, Park J, Kim YV, Nikolskaia O, Choi KS, Stins MF, and Kim KS (2005). "Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier". Infect Immun 73 (2): 1014-1022. PMID 15664945.
  64. ^ Ma Y, Sturrock A, and Weis JJ (1991). "Intracellular localization of Borrelia burgdorferi within human endothelial cells" (PDF). Infect Immun 59 (2): 671-678. PMID 1987083.
  65. ^ Klempner MS, Noring R, and Rogers RA (1993). "Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi". J Infect Dis 167 (5): 1074-1081. PMID 8486939.
  66. ^ Dorward DW, Fischer ER, and Brooks DM (1997). "Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme disease". Clin Infect Dis 25 Suppl 1: S2-8. PMID 9233657.
  67. ^ Montgomery RR, Nathanson MH, and Malawista SE (1993). "The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery". J Immunol 150 (3): 909-915. PMID 8423346.
  68. ^ Aberer E, Kersten A, Klade H, Poitschek C, and Jurecka W (2005 Aug 12-19). "Heterogeneity of Borrelia burgdorferi in the skin". Neurosci Lett. 384 (1-2): 112-116.
  69. ^ Girschick HJ, Huppertz HI, Russmann H, Krenn V, and Karch H (1996). "Intracellular persistence of Borrelia burgdorferi in human synovial cells". Rheumatol Int 16 (3): 125-132. PMID 8893378.
  70. ^ a b Nanagara R, Duray PH, and Schumacher HR Jr (1996). "Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms". Hum Pathol 27 (10): 1025-1034. PMID 8892586.
  71. ^ Livengood JA, Gilmore RD (2006). "Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi". Microbes Infect [Epub ahead of print]. PMID 17045505.
  72. ^ Georgilis K, Peacocke M, Klempner MS (1992). "Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro". J Infect Dis 166 (2): 440-444. PMID 1634816.
  73. ^ Brouqui P, Badiaga S, and Raoult D (1996). "Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin" (PDF). Antimicrob Agents Chemother 40 (6): 1552-1554. PMID 8726038.
  74. ^ a b Alban PS, Johnson PW, and Nelson DR (2000). "Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi". Microbiology 146 (Pt 1): 119-127. PMID 10658658.
  75. ^ a b Mursic VP, Wanner G, Reinhardt S, et al (1996). "Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants". Infection 24 (3): 218-226. PMID 8811359.
  76. ^ Kersten A, Poitschek C, Rauch S, and Aberer E (1995). "Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi" (PDF). Antimicrob Agents Chemother 39 (5): 1127-1133. PMID 7625800.
  77. ^ Schaller M, Neubert U (1994). "Ultrastructure of Borrelia burgdorferi after exposure to benzylpenicillin". Infection 22 (6): 401-406. PMID 7698837.
  78. ^ Phillips SE, Mattman LH, Hulinska D, and Moayad H (1998). "A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated". Infection 26 (6): 364-367. PMID 9861561.
  79. ^ Duray PH, Yin SR, Ito Y, et al (2005). "Invasion of human tissue ex vivo by Borrelia burgdorferi". J Infect Dis 191 (10): 1747-1754. PMID 15838803.
  80. ^ Gruntar I, Malovrh T, Murgia R, and Cinco M (2001). "Conversion of Borrelia garinii cystic forms to motile spirochetes in vivo". APMIS 109 (5): 383-388. PMID 11478686.
  81. ^ Murgia R and Cinco M (2004). "Induction of cystic forms by different stress conditions in Borrelia burgdorferi". APMIS 112 (1): 57-62. PMID 14961976.
  82. ^ Brorson O and Brorson SH (1999). "An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to metronidazole". APMIS 107 (6): 566-576. PMID 10379684.
  83. ^ Brorson O and Brorson SH (2004). "An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole" (PDF). Int Microbiol 7 (2): 139-142. PMID 15248163.
  84. ^ Brorson O and Brorson SH (2002). "An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine". Int Microbiol 5 (1): 25-31. PMID 12102233.
  85. ^ Liang FT, Yan J, Mbow ML, et al (2004). "Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses". Infect Immun 72 (10): 5759-5767. PMID 15385475.
  86. ^ Gilmore RD, Howison RR, Schmit VL, et al (2007). "Temporal expression analysis of the Borrelia burgdorferi paralogous gene family 54 genes BBA64, BBA65, and BBA66 during persistent infection in mice". Infect. Immun. 75 (6): 2753-2764. doi:10.1128/IAI.00037-07. PMID 17371862.
  87. ^ Schutzer SE, Coyle PK, Reid P, and Holland B (1999). "Borrelia burgdorferi-specific immune complexes in acute Lyme disease". JAMA 282 (20): 1942-1946. PMID 10580460.
  88. ^ Newman K Jr and Johnson RC (1984 month=Sep). "T-cell-independent elimination of Borrelia turicatae". Infect Immun. 45 (3): 572-576.
  89. ^ Dattwyler RJ, Thomas JA, Benach JL, and Golightly MG | title=Cellular immune response in Lyme disease: the response to mitogens, live Borrelia burgdorferi, NK cell function and lymphocyte subsets | journal=Zentralbl Bakteriol Mikrobiol Hyg [A] | year=1986 | month=Dec | volume=263 | issue=1-2 | pages=151-159}}
  90. ^ Kruger H, Pulz M, Martin R, and Sticht-Groh V (Sep-Oct 1990). "Long-term persistence of specific T- and B-lymphocyte responses to Borrelia burgdorferi following untreated neuroborreliosis". Infection 18 (5): 263-267.
  91. ^ Forsberg P, Ernerudh J, Ekerfelt C, Roberg M, Vrethem M, and Bergstrom S (Sep 1995). "The outer surface proteins of Lyme disease Borrelia spirochetes stimulate T cells to secrete interferon-gamma (IFN-gamma): diagnostic and pathogenic implications". Clin Exp Immunol. 101 (3): 453-460.
  92. ^ Yin Z, Braun J, Neure L, Wu P, Eggens U, Krause A, Kamradt T, and Sieper J (Jan 1997). "T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines". Arthritis Rheum. 40 (1): 69-79.
  93. ^ Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, and Ekerfelt C (Jan 2007). "Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals". Clin Exp Immunol. 147 (1): 18-27.
  94. ^ Olson CM, Hedrick MN, Izadi H, Bates TC, Olivera ER, and Anguita J (2006-10-30). "p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens". Infect Immun. 75 (1): 270-277.
  95. ^ Ramesh G and Philipp MT (2005 Aug 12-19). "Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins". Neurosci Lett. 384 (1-2): 112-116.
  96. ^ Singh SK, Girschick HJ (2006). "Toll-like receptors in Borrelia burgdorferi-induced inflammation". Clin. Microbiol. Infect. 12 (8): 705-17. doi:10.1111/j.1469-0691.2006.01440.x. PMID 16842565.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Lyme_disease_microbiology". A list of authors is available in Wikipedia.
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