Expression of Outer Surface Proteins A and C of Borrelia afzelii in Ixodes ricinus Ticks and in the Skin of Mice

Leuba-Garcia, S.; Galván-Martínez, Ricardo; Gern, Lise

doi:10.1016/s0934-8840(98)80187-4

Cited by 31 publications

(37 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of OSP gene products in the tick vector and the mammalian host has been studied previously (30). In unfed ticks, B burgdorferi usually expresses OspA and more rarely expresses OspC (31)(32)(33). Following attachment to the host and feeding, the spirochetes multiply, shed or down-regulate OspA, and up-regulate OspC within the tick (32,34).…”

Section: Discussionmentioning

confidence: 99%

“…Following attachment to the host and feeding, the spirochetes multiply, shed or down-regulate OspA, and up-regulate OspC within the tick (32,34). This pattern of OSP gene expression is probably maintained both during transmission to and in the early phase of infection in the mammalian host (29,32,33). In persisting infections it is thought that a reversal eventually occurs, with OspA being up-regulated and OspC down-regulated.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

Batsford

Dunn

Mihatsch³

2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To examine the ability of bacterial lipoproteins from the spirochete Borrelia burgdorferi to cause in vivo tissue injury (arthritis).Methods. Outer surface proteins (OSPs) from B burgdorferi were used in a rat model of antigen-induced allergic arthritis. Intraarticular challenge with recombinant OspA, OspB, and OspC in nonlipidated (peptide) and lipidated forms was performed in the left knee joint; the contralateral joint received buffer as control. Inflammation was monitored by technetium scintigraphy and histology.Results. Nonlipidated (peptide) OspA, OspB, and OspC did not induce arthritis; the only exception was polymerized OspA, which was tested in preimmunized rats. Lipidated OspA from 2 different strains and lipidated OspC induced severe arthritis, whereas lipidated OspB failed to induce injury. A synthetic analog of the OSP lipid modification, lipopeptide Pam 3 Cys-SerLys 4 -OH, either alone or coupled to bovine serum albumin, also failed to induce injury. Injury did not develop in control groups that were given the appropriate buffers or lipopolysaccharide. This showed that lipidated borrelial OSPs can be potent arthritogens but vary greatly with respect to their injury-inducing potential. The possession of a lipid modification is essential but is not sufficient to render an OSP arthritogenic.Conclusion. This is the first study to demonstrate that individual lipoproteins from B burgdorferi can induce experimental joint injury in vivo. These results may help elucidate the pathogenesis of Lyme arthritis and, above all, underline the importance of bacterial lipoproteins as major virulence factors.Lipoproteins are now being recognized as prime virulence factors of bacteria. For many decades this group of molecules played the role of poor relation to the lipopolysaccharides (LPS), but particularly the discovery that lipoproteins can act as ligands for the Toll-like receptor (TLR) complex has rekindled interest (1). In earlier studies, a number of naturally occurring bacterial lipoproteins and their synthetic lipopeptide analogs were shown to possess impressive biologic activities. The Braun protein, a prototype lipoprotein, can stimulate lymphocytes (2), and the corresponding synthetic lipopeptide is in fact now used as an adjuvant (3). Membrane lipoproteins and the corresponding lipopeptides from mycoplasma could induce mononuclear phagocytes to secrete cytokines; a particular lipopeptide from Mycoplasma fermentans, macrophage activating lipopeptide 2, was effective even at concentrations in the picogram range (4). The outer surface lipoproteins (OSPs) of Borrelia burgdorferi have been shown to exhibit similar stimulatory effects (5-8).Results of recent in vitro studies indicated that the lipid moiety plays a key role, and that the CD14/ TLR-2 receptors can be involved (9-11). Lipoproteins have been shown to be capable of inducing tissue injury in animals, mimicking certain common clinical manifestations of the corresponding infection in man. First, synthetic lipopeptide analogs of treponemal and...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

Batsford

Dunn

Mihatsch³

2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…It has proven difficult to directly examine the Osp phenotype of spirochetes in mouse skin during tick transmission because of the difficulty of finding bacteria in the skin. However, in one study OspC-positive spirochetes have been observed in the skin of mice infected by tick bite (27). The hypostome is a tick mouth part armed with numerous, sharp, curved denticles and is inserted into the host dermis during tick feeding (28).…”

Section: B Burgdorferi In the Mouse Dermis At The Site Of Tick Attacmentioning

confidence: 99%

Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks

Ohnishi

Piesman²,

Silva

2001

Proc. Natl. Acad. Sci. U.S.A.

278

303

View full text Add to dashboard Cite

The genome of Borrelia burgdorferi encodes a large number of lipoproteins, many of which are expressed only at certain stages of the spirochete's life cycle. In the current study we describe the B. burgdorferi population structure with respect to the production of two lipoproteins [outer surface protein A (OspA) and outer surface protein C (OspC)] during transmission from the tick vector to the mammalian host. Before the blood meal, the bacteria in the tick were a homogeneous population that mainly produced OspA only. During the blood meal, the population became more heterogeneous; many bacteria produced both OspA and OspC, whereas others produced only a single Osp and a few produced neither Osp. From the heterogeneous spirochetal population in the gut, a subset depleted of OspA entered the salivary glands and stably infected the host at time points >53 hr into the blood meal. We also examined genetic heterogeneity at the B. burgdorferi vlsE locus before and during the blood meal. In unfed ticks, the vlsE locus was stable and one predominant and two minor alleles were detected. During the blood meal, multiple vlsE alleles were observed in the tick. Tick feeding may increase recombination at the vlsE locus or selectively amplify rare vlsE alleles present in unfed ticks. On the basis of our data we propose a model, which is different from the established model for B. burgdorferi transmission. Implicit in our model is the concept that tick transmission converts a homogeneous spirochete population into a heterogeneous population that is poised to infect the mammalian host.

show abstract

“…complex comprises at least three human-pathogenic species in Europe, B. burgdorferi sensu stricto (s.s.), the only species causing Lyme disease in the United States, Borrelia afzelii, and Borrelia garinii (Baranton et al, 1992;Burgdorfer et al, 1982;Wang et al, 1999). These spirochetes are maintained in their natural setting through complex enzootic cycles between warm-blooded hosts and ixodid tick vectors (Benach et al, 1987;de Silva and Fikrig, 1995;Gern et al, 1990;Leuba-Garcia et al, 1998;Ribeiro et al, 1987;Schwan and Piesman, 2000). During tick feeding, B. burgdorferi migrates through the gut wall, disseminates and invades various tissues, including the salivary glands wherefrom they are transmitted to the host by saliva.…”

Section: Introductionmentioning

confidence: 99%

Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus

Fingerle

Goettner

Gern

et al. 2007

International Journal of Medical Microbiology

Self Cite

View full text Add to dashboard Cite

Alteration of the outer surface protein (Osp) composition -especially that of OspA and OspC -seems to be important for the adaptation of Borrelia burgdorferi sensu lato to its endothermic hosts (mammals) and poikilothermic vectors (ticks). OspA possibly mediates adherence to tick midgut cells thus enabling the borreliae to survive in the vector, while OspC is associated with borrelial invasion of the tick salivary glands and infection of the mammalian hosts. Here we describe the first successful transformation and complementation of a Borrelia afzelii ospC mutant with the wild-type ospC in trans. To test the influence of OspC on the dissemination behavior in ticks, unfed Ixodes ricinus nymphs were artificially infected by capillary feeding either with B. afzelii wild type, the B. afzelii ospC mutant or the ospC-complemented clone. Tick midguts and salivary glands were investigated after different time intervals for the presence of borreliae and for OspA and OspC by immunfluorescence staining with monoclonal antibodies. While the B. afzelii wild-type strain exhibiting abundant OspC on its surface disseminated to the salivary glands, the OspCnegative mutant was only present in the tick midguts. The ospC-complemented clone which constitutively expresses the wild-type ospC was again able to colonize the salivary glands. This finding demonstrates that OspC is crucial for dissemination of B. afzelii from the tick midgut to the salivary glands, a prerequisite for infection of the warm-blooded host. A summary of the detailed data presented here has already been given in Goettner et al.

show abstract

Expression of Outer Surface Proteins A and C of Borrelia afzelii in Ixodes ricinus Ticks and in the Skin of Mice

Cited by 31 publications

References 30 publications

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks

Complementation of a Borrelia afzelii OspC mutant highlights the crucial role of OspC for dissemination of Borrelia afzelii in Ixodes ricinus

Contact Info

Product

Resources

About