Infection of Syrian hamsters with Lyme disease spirochetes

Johnson, Russell C.; Marek, Natalia; Kodner, Carrie

doi:10.1128/jcm.20.6.1099-1101.1984

Cited by 187 publications

(98 citation statements)

References 10 publications

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“…In early studies of this organism, it was determined that its genome consisted of a linear chromosome and multiple linear and circular plasmids ranging in size from 56 kbp to 5 kbp. Many of these plasmids were easily lost during in vitro culture, and absence of some of these plasmids correlated with loss of infectivity in animal models (15)(16)(17)(18)(19)(20)(21)(22)(23). The availability of the genome sequence of B. burgdorferi B31 showed that the organism contained 12 linear and 9 circular plasmids (with a total of over 600 kbp) as well as a 972 kbp linear chromosome (24,25).…”

Section: Vls System Of B Burgdorferi B31mentioning

confidence: 99%

vlsAntigenic Variation Systems of Lyme DiseaseBorrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity

Norris

2015

Mobile DNA III

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Spirochetes that cause Lyme borreliosis (also called Lyme disease) possess the vls locus, encoding an elaborate antigenic variation system. This locus contains the expression site vlsE as well as a contiguous array of vls silent cassettes, which contain variations of the central cassette region of vlsE. The locus is present on one of the many linear plasmids in the organism, e.g. plasmid lp28-1 in the strain B. burgdorferi B31. Changes in the sequence of vlsE occur continuously during mammalian infection and consist of random, segmental, unidirectional recombination events between the silent cassettes and the cassette region of vlsE. These gene conversion events do not occur during in vitro culture or the tick portion of the infection cycle of Borrelia burgdorferi or the other related Borrelia species that cause Lyme disease. The mechanism of recombination is largely unknown, but requires the RuvAB Holliday junction branch migrase. Other features of the vls locus also appear to be required, including cis locations of vlsE and the silent cassettes and high G+C content and GC skew. The vls system is required for long-term survival of Lyme Borrelia in infected mammals and represents an important mechanism of immune evasion. In addition to sequence variation, immune selection also results in significant heterogeneity in the sequence of the surface lipoprotein VlsE. Despite antigenic variation, VlsE generates a robust antibody response, and both full length VlsE and the C6 peptide (corresponding to invariant region 6) are widely used in immunodiagnostic tests for Lyme disease.Antigenic variation is defined as a hereditable, reversible variation in an antigenic structure that occurs during the course of infection at a rate higher than would be expected for standard recombination or mutation mechanisms. Many bacterial and protozoal pathogens have developed antigenic variation systems in which surface antigens can be continually altered as a means of evading the constant onslaught of adaptive antibody and T cell responses (1). In 1997, an elaborate antigenic variation system was identified in B. burgdorferi B31 (2). Because of sequence similarity between this system and the previously characterized Variable Major Protein (VMP) system of relapsing fever bacteria, it was termed the VMP-like sequence (vls) locus. Its expression site, called vls Expressed (vlsE), undergoes remarkable sequence variation involving segmental gene conversion events from vls silent cassettes. This chapter will describe what is currently known about the structure,

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Section: Vls System Of B Burgdorferi B31mentioning

confidence: 99%

vlsAntigenic Variation Systems of Lyme DiseaseBorrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity

Norris

2015

Mobile DNA III

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“…Sera were collected one week later, and the development of antibody against the corresponding borrelial antigen was confirmed by ELISA and immunoblot analysis (not shown). Each group of hamsters was then challenged with a single intraperitoneal injection of B. burgdor-feri (10 8 cells/animal), as previously described [30]. Twelve days post challenge, the hamsters were sacrificed and spirochete levels were measured in the joint, heart and bladder samples by quantitative PCR.…”

Section: Immunization Of Hamsters With Ndv-vectored Bmpa Interferes Wmentioning

confidence: 99%

“…Signs of arthritis and carditis become apparent at 2-3 weeks and then resolve after 7-8 weeks although mice remain infected for months. Similar to mice, hamsters of both sexes and all ages are susceptible to disseminated infection [30,31]. The use of hamsters as a rodent model of Lyme borreliosis gained immediate attention following discovery of the disease.…”

Section: Introductionmentioning

confidence: 99%

A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen

Xiao

Kumar

Yang

et al. 2011

Vaccine

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Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two Borrelia burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. In contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (108 cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease.

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“…Lyme disease spirochetes grow only in extremely rich, undefined medium, and take one to several weeks to form a visible colony (Barbour, 1984;Elias et al ., 2002). In addition, in vitro culture is associated with variable loss of plasmids and a concomitant loss of infectivity (Johnson et al ., 1984;Barbour, 1988;Simpson et al ., 1990;Norris et al ., 1995;Purser and Norris, 2000;Labandeira-Rey and Skare, 2001). In part because of the problematic nature of in vitro culture, genetic manipulation of these bacteria has been difficult, and genetic approaches similar to those used to study most other bacterial pathogens have not been possible for Lyme disease spirochetes, much to the frustration of investigators in the field.…”

Section: Lyme Disease and The Biology Of Borrelia Burgdorferimentioning

confidence: 99%

Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete

Coburn

Fischer

Leong

2005

Molecular Microbiology

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SummaryThe Lyme disease spirochetes, comprised of at least three closely related species, Borrelia burgdorferi , Borrelia garinii and Borrelia afzelii , are fascinating and enigmatic bacterial pathogens. They are maintained by tick-mediated transmission between mammalian hosts, usually small rodents. The ability of these bacteria, which have relatively small genomes, to survive and disseminate in both an immunocompetent mammal and in an arthropod vector suggests that they have evolved elegant and indispensable strategies for interacting with their hosts. Recognition of specific mammalian and tick tissues is likely to be essential for successful completion of the enzootic life cycle but, given the historical difficulties in genetic manipulation of these organisms, characterization of factors promoting cell adhesion has until recently largely been confined to either the manipulation of host cells or the analysis of potential bacterial ligands in the form of recombinant proteins. These studies have led to the identification of several mammalian receptors for Lyme disease spirochetes, including glycosaminoglycans, decorin, fibronectin and integrins, as well as a tick receptor for the bacterium, and also candidate cognate bacterial ligands. Recent advances in our ability to genetically manipulate Lyme disease spirochetes, particularly B. burgdorferi , are now providing us with firm evidence that these ligands indeed do promote bacterial adherence to host cells, and with new insights into the roles of these multifacted Borrelia -host cell interactions during mammalian and arthropod infection.

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Infection of Syrian hamsters with Lyme disease spirochetes

Cited by 187 publications

References 10 publications

vlsAntigenic Variation Systems of Lyme DiseaseBorrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity

vlsAntigenic Variation Systems of Lyme DiseaseBorrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity

A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen

Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete

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